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Individuals with schizophrenia (SZ) and auditory hallucinations (AHs) display a distorted sense of self and self-other boundaries. Alterations of activity in midline cortical structures such as the prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) during self-reference as well as in the superior temporal gyrus (STG) have been proposed as neuromarkers of SZ and AHs. In this randomized, participant-blinded, sham-controlled trial, 22 adults (18 males) with SZ spectrum disorders (SZ or schizoaffective disorder) and frequent medication-resistant AHs received one session of real-time fMRI neurofeedback (NFB) either from the STG (n = 11; experimental group) or motor cortex (n = 11; control group). During NFB, participants were instructed to upregulate their STG activity by attending to pre-recorded sentences spoken in their own voice and downregulate it by ignoring unfamiliar voices. Before and after NFB, participants completed a self-reference task where they evaluated if trait adjectives referred to themselves (self condition), Abraham Lincoln (other condition), or whether adjectives had a positive valence (semantic condition). FMRI activation analyses of self-reference task data tested between-group changes after NFB (self>semantic, post>pre-NFB, experimental>control). Analyses were pre-masked within a self-reference network. Activation analyses revealed significantly (p < 0.001) greater activation increase in the experimental, compared to the control group, after NFB within anterior regions of the self-reference network (mPFC, ACC, superior frontal cortex). STG-NFB was associated with activity increase in the mPFC, ACC, and superior frontal cortex during self-reference. Modulating the STG is associated with activation changes in other, not-directly targeted, regions subserving higher-level cognitive processes associated with self-referential processes and AHs psychopathology in SZ. Rt-fMRI Neurofeedback and AH in Schizophrenia; https://clinicaltrials.gov/study/NCT03504579. [ABSTRACT FROM AUTHOR]

Mindfulness training (MT) reduces self-referential processing and promotes interoception, the perception of sensations from inside the body, by increasing ones 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.

Abstract Background Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. Methods Adolescents (N = 90) with a current diagnosis of MDD ages 13–18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 min of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-min mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. Discussion Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. Trial Registration This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495).

Background: Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. Methods: Adolescents (N = 90) with a current diagnosis of MDD ages 13–18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 min of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-min mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. Discussion: Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. Trial Registration: This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495). [ABSTRACT FROM AUTHOR]

Abstract A wide variety of model systems and experimental techniques can provide insight into the structure and function of the human brain in typical development and in neurodevelopmental disorders. Unfortunately, this work, whether based on manipulation of animal models or observational and correlational methods in humans, has a high attrition rate in translating scientific discovery into practicable treatments and therapies for neurodevelopmental disorders. With new computational and neuromodulatory approaches to interrogating brain networks, opportunities exist for “bedside-to bedside-translation” with a potentially shorter path to therapeutic options. Specifically, methods like lesion network mapping can identify brain networks involved in the generation of complex symptomatology, both from acute onset lesion-related symptoms and from focal developmental anomalies. Traditional neuroimaging can examine the generalizability of these findings to idiopathic populations, while non-invasive neuromodulation techniques such as transcranial magnetic stimulation provide the ability to do targeted activation or inhibition of these specific brain regions and networks. In parallel, real-time functional MRI neurofeedback also allow for endogenous neuromodulation of specific targets that may be out of reach for transcranial exogenous methods. Discovery of novel neuroanatomical circuits for transdiagnostic symptoms and neuroimaging-based endophenotypes may now be feasible for neurodevelopmental disorders using data from cohorts with focal brain anomalies. These novel circuits, after validation in large-scale highly characterized research cohorts and tested prospectively using noninvasive neuromodulation and neurofeedback techniques, may represent a new pathway for symptom-based targeted therapy.

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. [ABSTRACT FROM AUTHOR]

A wide variety of model systems and experimental techniques can provide insight into the structure and function of the human brain in typical development and in neurodevelopmental disorders. Unfortunately, this work, whether based on manipulation of animal models or observational and correlational methods in humans, has a high attrition rate in translating scientific discovery into practicable treatments and therapies for neurodevelopmental disorders. With new computational and neuromodulatory approaches to interrogating brain networks, opportunities exist for "bedside-to bedside-translation" with a potentially shorter path to therapeutic options. Specifically, methods like lesion network mapping can identify brain networks involved in the generation of complex symptomatology, both from acute onset lesion-related symptoms and from focal developmental anomalies. Traditional neuroimaging can examine the generalizability of these findings to idiopathic populations, while non-invasive neuromodulation techniques such as transcranial magnetic stimulation provide the ability to do targeted activation or inhibition of these specific brain regions and networks. In parallel, real-time functional MRI neurofeedback also allow for endogenous neuromodulation of specific targets that may be out of reach for transcranial exogenous methods. Discovery of novel neuroanatomical circuits for transdiagnostic symptoms and neuroimaging-based endophenotypes may now be feasible for neurodevelopmental disorders using data from cohorts with focal brain anomalies. These novel circuits, after validation in large-scale highly characterized research cohorts and tested prospectively using noninvasive neuromodulation and neurofeedback techniques, may represent a new pathway for symptom-based targeted therapy. [ABSTRACT FROM AUTHOR]

Brain–computer interfaces (BCIs) can be used in real-time fMRI neurofeedback (rtfMRI NF) investigations to provide feedback on brain activity to enable voluntary regulation of the blood-oxygen-level dependent (BOLD) signal from localized brain regions. However, the temporal pattern of successful self-regulation is dynamic and complex. In particular, the general linear model (GLM) assumes fixed temporal model functions and misses other dynamics. We propose a novel data-driven analyses approach for rtfMRI NF using intersubject covariance (ISC) analysis. The potential of ISC was examined in a reanalysis of data from 21 healthy individuals and nine patients with post-traumatic stress-disorder (PTSD) performing up-regulation of the anterior cingulate cortex (ACC). ISC in the PTSD group differed from healthy controls in a network including the right inferior frontal gyrus (IFG). In both cohorts, ISC decreased throughout the experiment indicating the development of individual regulation strategies. ISC analyses are a promising approach to reveal novel information on the mechanisms involved in voluntary self-regulation of brain signals and thus extend the results from GLM-based methods. ISC enables a novel set of research questions that can guide future neurofeedback and neuroimaging investigations. [ABSTRACT FROM AUTHOR]

Affective disorders are associated with maladaptive emotion regulation strategies. In particular, the left more than the right ventrolateral prefrontal cortex (vlPFC) may insufficiently regulate emotion processing, e.g., in the amygdala. A double-blind cross-over study investigated NF-supported cognitive reappraisal training in major depression (n = 42) and age- and gender-matched controls (n = 39). In a randomized order, participants trained to upregulate either the left or the right vlPFC during cognitive reappraisal of negative images on two separate days. We wanted to confirm regional specific NF effects with improved learning for left compared to right vlPFC (ClinicalTrials.gov NCT03183947). Brain responses and connectivity were studied with respect to training progress, gender, and clinical outcomes in a 4-week follow-up. Increase of vlPFC activity was stronger after NF training from the left- than the right-hemispheric ROI. This regional-specific NF effect during cognitive reappraisal was present across patients with depression and controls and supports a central role of the left vlPFC for cognitive reappraisal. Further, the activity in the left target region was associated with increased use of cognitive reappraisal strategies (r = 0.48). In the 4-week follow-up, 75% of patients with depression reported a successful application of learned strategies in everyday life and 55% a clinically meaningful symptom improvement suggesting clinical usability.

Affective disorders are associated with maladaptive emotion regulation strategies. In particular, the left more than the right ventrolateral prefrontal cortex (vlPFC) may insufficiently regulate emotion processing, e.g., in the amygdala. A double-blind cross-over study investigated NF-supported cognitive reappraisal training in major depression (n = 42) and age- and gender-matched controls (n = 39). In a randomized order, participants trained to upregulate either the left or the right vlPFC during cognitive reappraisal of negative images on two separate days. We wanted to confirm regional specific NF effects with improved learning for left compared to right vlPFC (ClinicalTrials.gov NCT03183947). Brain responses and connectivity were studied with respect to training progress, gender, and clinical outcomes in a 4-week follow-up. Increase of vlPFC activity was stronger after NF training from the left- than the right-hemispheric ROI. This regional-specific NF effect during cognitive reappraisal was present across patients with depression and controls and supports a central role of the left vlPFC for cognitive reappraisal. Further, the activity in the left target region was associated with increased use of cognitive reappraisal strategies (r = 0.48). In the 4-week follow-up, 75% of patients with depression reported a successful application of learned strategies in everyday life and 55% a clinically meaningful symptom improvement suggesting clinical usability. [ABSTRACT FROM AUTHOR]

Background: Small hippocampal volume is a prevalent neurostructural abnormality in posttraumatic stress disorder (PTSD). However, whether the hippocampal atrophy is the cause of disease symptoms or a pre-existing risk factor and whether it is a reversible alteration or a permanent trait are unclear. The trait- or state-dependent alteration could also differ among the hippocampal subfields.Methods: The study examined the longitudinal hippocampal volume changes due to positive emotional training with left amygdala (LA) real-time fMRI neurofeedback (rtfMRI-nf) in combat veterans with PTSD. The participants were trained to increase the neurofeedback signal from LA (experimental group, N = 20) or brain region not involved in emotion processing (control group, N = 9) by recalling a positive autobiographical memory. The pre- and post-training structural MRI brain images were processed with FreeSurfer to evaluate the hippocampal subfield volumes. Hippocampal volumes for healthy controls (N = 43) were also examined to evaluate the baseline abnormality in PTSD.Results: A significant group difference in volume change was found in the left CA1 head region. This region had the most significant volume reduction at the baseline in PTSD. The experimental group showed a significant volume increase, while the control group showed a significant volume decrease in this region. The volume change in the control group negatively correlated with interval days between the scans.Limitations: A cognitive improvement due to the hippocampal volume increase could not be found with symptom scales.Conclusions: RtfMRI-nf positive emotional training increased the hippocampus volume among people with PTSD, suggesting that hippocampal atrophy in PTSD is modifiable. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

Background: Traumatic experiences are associated with neurofunctional dysregulations in key regions of the emotion regulation circuits. In particular, amygdala responsivity to negative stimuli is exaggerated while engagement of prefrontal regulatory control regions is attenuated. Successful application of emotion regulation (ER) strategies may counteract this disbalance, however, application of learned strategies in daily life is hampered in individuals afflicted by posttraumatic stress disorder (PTSD). We hypothesized that a single session of real-time fMRI (rtfMRI) guided upregulation of prefrontal regions during an emotion regulation task enhances self-control during exposure to negative stimuli and facilitates transfer of the learned ER skills to daily life. Methods: In a cross-over design, individuals with a PTSD diagnosis after a single traumatic event (n = 20) according to DSM-IV-TR criteria and individuals without a formal psychiatric diagnosis (n = 21) underwent a cognitive reappraisal training. In randomized order, all participants completed two rtfMRI neurofeedback (NF) runs targeting the left lateral prefrontal cortex (lPFC) and two control runs without NF (NoNF) while using cognitive reappraisal to reduce their emotional response to negative scenes. During the NoNF runs, two %%-signs were displayed instead of the two-digit feedback (FB) to achieve a comparable visual stimulation. The project aimed at defining the clinical potential of the training according to three success markers: (1) NF induced changes in left lateral prefrontal cortex and bilateral amygdala activity during the regulation of aversive scenes compared to cognitive reappraisal alone (primary registered outcome), (2) associated changes on the symptomatic and behavioral level such as indicated by PTSD symptom severity and affect ratings, (3) clinical utility such as indicated by perceived efficacy, acceptance, and transfer to daily life measured four weeks after the training. Results: In comparison to the reappraisal without feedback, a neurofeedback-specific decrease in the left lateral PFC (d = 0.54) alongside an attenuation of amygdala responses (d = 0.33) emerged. Reduced amygdala responses during NF were associated with symptom improvement (r = −0.42) and less negative affect (r = −0.63) at follow-up. The difference in symptom scores exceeds requirements for a minimal clinically important difference and corresponds to a medium effect size (d = 0.64). Importantly, 75% of individuals with PTSD used the strategies in daily life during a one-month follow-up period and perceived the training as efficient. Conclusion: Our findings suggest beneficial effects of the NF training indicated by reduced amygdala responses that were associated with improved symptom severity and affective state four weeks after the NF training as well as patient-centered perceived control during the training, helpfulness and application of strategies in daily life. However, reduced prefrontal involvement was unexpected. The study suggests good tolerability of the training protocol and potential for clinical use in the treatment of PTSD.

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.

Background: Brooding is a critical symptom and prognostic factor of major depressive disorder (MDD), which involves passively dwelling on self-referential dysphoria and related abstractions. The neurobiology of brooding remains under characterized. We aimed to elucidate neural dynamics underlying brooding, and explore their responses to neurofeedback intervention in MDD., Methods: We investigated functional MRI (fMRI) dynamic functional network connectivity (dFNC) in 36 MDD subjects and 26 healthy controls (HCs) during rest and brooding. Rest was measured before and after fMRI neurofeedback (MDD-active/sham: n=18/18, HC-active/sham: n=13/13). Baseline brooding severity was recorded using Ruminative Response Scale - Brooding subscale (RRS-B)., Results: Four recurrent dFNC states were identified. Measures of time spent were not significantly different between MDD and HC for any of these states during brooding or rest. RRS-B scores in MDD showed significant negative correlation with measures of time spent in dFNC state 3 during brooding (r=-0.5, p= 1.7E-3, FDR-significant). This state comprises strong connections spanning several brain systems involved in sensory, attentional and cognitive processing. Time spent in this anti-brooding dFNC state significantly increased following neurofeedback only in the MDD active group (z=-2.09, p=0.037)., Limitations: The sample size was small and imbalanced between groups. Brooding condition was not examined post-neurofeedback., Conclusion: We identified a densely connected anti-brooding dFNC brain state in MDD. MDD subjects spent significantly longer time in this state after active neurofeedback intervention, highlighting neurofeedback's potential for modulating dysfunctional brain dynamics to treat MDD., Competing Interests: Declaration of Competing Interest The authors report no declarations of competing interests.

The triple networks, namely the default-mode network (DMN), the central executive network (CEN), and the salience network (SN), play crucial roles in disorders of the brain, as well as in basic neuroscientific processes such as mindfulness. However, currently, there is no consensus on the underlying functional features of the triple networks associated with mindfulness. In this study, we tested the hypothesis that (a) the partial regression coefficient (i.e., slope): from the SN to the DMN, mediated by the CEN, would be one of the potential mindfulness features in the real-time functional magnetic resonance imaging (rtfMRI) neurofeedback (NF) setting, and (b) this slope level may be enhanced by rtfMRI-NF training. Sixty healthy mindfulness-naïve males participated in an MRI session consisting of two non-rtfMRI-runs, followed by two rtfMRI-NF runs and one transfer run. Once the regions-of-interest of each of the triple networks were defined using the non-rtfMRI-runs, the slope level was calculated by mediation analysis and used as neurofeedback information, in the form of a thermometer bar, to assist with participant mindfulness during the rtfMRI-NF runs. The participants were asked to increase the level of the thermometer bar while deploying a mindfulness strategy, which consisted of focusing attention on the physical sensations of breathing. rtfMRI-NF training was conducted as part of a randomized controlled trial design, in which participants were randomly assigned to either an experimental group or a control group. The participants in the experimental group received contingent neurofeedback information, which was obtained from their own brain signals, whereas the participants in the control group received non-contingent neurofeedback information that originated from matched participants in the experimental group. Our results indicated that the slope level from the SN to the DMN, mediated by the CEN, was associated with mindfulness score (rtfMRI-NF runs: r = 0.53, p = 0.007; p -value was corrected from 10,000 random permutations) and with task-performance feedback score (rtfMRI-NF run: r = 0.61, p = 0.001) in the experimental group only. In addition, during the rtfMRI-NF runs the level of the partial regression coefficient feature was substantially increased in the experimental group compared to the control group (p < 0.05 from the paired t -test; the p -value was corrected from 10,000 random permutations). To the best of our knowledge, this is the first study to demonstrate a partial regression coefficient feature of mindfulness in the rtfMRI-NF setting obtained by triple network mediation analysis, as well as the possibility of enhancement of the partial regression coefficient feature by rtfMRI-NF training. • Mediation analysis using triple networks was employed to estimate functional feature of mindfulness (MF). • Real-time fMRI (rtfMRI) neurofeedback (NF) training based on this functional feature of MF was presented. • The partial regression coefficient from the SN to the DMN, mediated by the CEN appeared to be a potential feature of MF. • The validity of this functional feature of MF was evaluated by comparing alternative functional connectivity levels in the triple networks. • The possibility of enhancement of this functional feature of MF was demonstrated via rtfMRI-NFbased training. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 i.e. 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 feedback signal 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 versus 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 towards 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 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.

Psychiatric conditions of emotion dysregulation are often characterized by difficulties in regulating the activity of limbic regions such as the amygdala. Real-time functional magnetic resonance imaging (rt-fMRI) allows to feedback brain activation and opens the possibility to establish a neurofeedback (NF) training of amygdala activation, e.g. for subjects suffering from emotion dysregulation.As a first step, we investigated whether feedback of the amygdala response to aversive scenes can improve down-regulation of amygdala activation. One group of healthy female participants received amygdala feedback (N=16) and a control group was presented with feedback from a control region located in the basal ganglia (N(sum)=32). Subjects completed a one-session rt-fMRI-NF training where they viewed aversive pictures and received continuous visual feedback on brain activation (REGULATE condition). In a control condition, subjects were advised to respond naturally to aversive pictures (VIEW), and a neutral condition served as the non-affective control (NEUTRAL). In an adjacent run, subjects were presented with aversive pictures without feedback to test for transfer effects of learning.In a region of interest (ROI) analysis, the VIEW and the REGULATE conditions were contrasted to estimate brain regulation success. The ROI analysis was complemented by an exploratory analysis of activations at the whole brain level. Both groups showed down-regulation of the amygdala response during training. Feedback from the amygdala but not from the control region was associated with down-regulation of the right amygdala in the transfer test. The whole-brain analysis did not detect significant group interactions. Results of the group whole-brain analyses are discussed.We present a proof-of-concept study using rt-fMRI-NF for amygdala down-regulation in the presence of aversive scenes. Results are in line with a potential benefit of neurofeedback training for amygdala regulation.

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. [ABSTRACT FROM AUTHOR]

Psychiatric conditions of emotion dysregulation are often characterized by difficulties in regulating the activity of limbic regions such as the amygdala. Real-time functional magnetic resonance imaging (rt-fMRI) allows to feedback brain activation and opens the possibility to establish a neurofeedback (NF) training of amygdala activation, e.g., for subjects suffering from emotion dysregulation. As a first step, we investigated whether feedback of the amygdala response to aversive scenes can improve down-regulation of amygdala activation. One group of healthy female participants received amygdala feedback (N = 16) and a control group was presented with feedback from a control region located in the basal ganglia [N(sum) = 32]. Subjects completed a one-session rt-fMRI-NF training where they viewed aversive pictures and received continuous visual feedback on brain activation (REGULATE condition). In a control condition, subjects were advised to respond naturally to aversive pictures (VIEW), and a neutral condition served as the non-affective control (NEUTRAL). In an adjacent run, subjects were presented with aversive pictures without feedback to test for transfer effects of learning. In a region of interest (ROI) analysis, the VIEW and the REGULATE conditions were contrasted to estimate brain regulation success. The ROI analysis was complemented by an exploratory analysis of activations at the whole-brain level. Both groups showed down-regulation of the amygdala response during training. Feedback from the amygdala but not from the control region was associated with down-regulation of the right amygdala in the transfer test. The whole-brain analysis did not detect significant group interactions. Results of the group whole-brain analyses are discussed.We present a proof-of-concept study using rt-fMRI-NF for amygdala down-regulation in the presence of aversive scenes. Results are in line with a potential benefit of NF training for amygdala regulation. [ABSTRACT FROM AUTHOR]