Amygdala Neurofeedback for Depression
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Kymberly Young
Must be taking: SSRI antidepressants
Must not be taking: Antipsychotics, Anticonvulsants, Stimulants, others
Disqualifiers: Cardiovascular, Substance dependence, Brain injury, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
The purpose of this study is to determine the clinical efficacy of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training to increase the amygdala's response to positive autobiographical memories in patients with depression who are considered treatment-resistant
Will I have to stop taking my current medications?
You can continue taking your current SSRI antidepressant if it's stable for at least 3 weeks. However, you must stop taking any antipsychotics, anticonvulsants, stimulants, benzodiazepines, beta-blockers, or other medications that might affect brain blood flow at least 3 weeks before the trial.
What data supports the effectiveness of the treatment Amygdala Neurofeedback for Depression?
Research shows that Amygdala Neurofeedback, which involves training the brain to respond more positively using real-time brain imaging, can help reduce symptoms of depression. Studies found that this treatment can improve emotional processing and increase brain connectivity, leading to better mood regulation in people with depression.12345
Is Amygdala Neurofeedback safe for humans?
Research on real-time functional MRI neurofeedback (rtfMRI-NF) involving the amygdala has been conducted with healthy participants and those with a history of depression, showing that it can help regulate brain activity without reported safety issues. These studies suggest that the technique is generally safe for human use.13678
How is Amygdala Neurofeedback treatment different from other treatments for depression?
Amygdala Neurofeedback is unique because it uses real-time brain imaging to help individuals learn to control their brain activity, specifically targeting the amygdala, which is involved in emotional processing. This approach is different from traditional treatments like medication or talk therapy, as it directly trains the brain to improve emotional regulation and processing of positive information.123910
Eligibility Criteria
This trial is for right-handed adults aged 18-55 with Major Depressive Disorder (MDD) who haven't improved after two SSRI treatments. Participants can be unmedicated or on a stable SSRI regimen, must experience anhedonia, and have difficulty recalling specific positive memories. Exclusions include other major psychiatric disorders, recent substance dependence, traumatic brain injury, MRI incompatibility (like claustrophobia), pregnancy, breastfeeding, non-English speakers, vision issues without correction, and certain unstable medical conditions.Inclusion Criteria
must have fewer than 45% memories categorized as specific on the Autobiographical Memory Test
I have tried two SSRI medications without success.
I am right-handed, aged 18-55, with diagnosed recurrent major depression and currently feeling depressed.
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Exclusion Criteria
are unable to complete questionnaires written in English
You cannot have an MRI scan due to feeling very uncomfortable in small or enclosed spaces (claustrophobia) or having certain metal objects inside your body.
I do not have any serious or unstable health conditions.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive 5 sessions of real-time fMRI neurofeedback training over a 2-month period
8 weeks
Follow-up
Participants are monitored for changes in amygdala activity and clinical symptoms after treatment
4 weeks
Treatment Details
Interventions
- Amygdala Neurofeedback (Behavioral Intervention)
- Parietal Neurofeedback (Behavioral Intervention)
Trial OverviewThe study tests if neurofeedback using real-time fMRI can help patients with treatment-resistant depression by enhancing the amygdala's response to positive memories. It involves two types of neurofeedback: one targeting the parietal region and another focusing on the amygdala of the brain.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Amygdala NeurofeedbackExperimental Treatment1 Intervention
attempt to up regulate the left amygdala during positive autobiographical memory recall via real time fMRI neurofeedback from the amygdala. Five sessions will be performed within a 2 month period.
Group II: Parietal NeurofeedbackActive Control1 Intervention
attempt to upregulate the left horizontal segment of the intraparietal sulcus, a region not involved in emotional processing, during positive autobiographical memory recall via real time fMRI neurofeedback. Five sessions will be performed within a 2 month period.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PittsburghPittsburgh, PA
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Who Is Running the Clinical Trial?
Kymberly YoungLead Sponsor
University of PittsburghLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
Enhanced efficacy of CBT following augmentation with amygdala rtfMRI neurofeedback in depression. [2023]Despite cognitive behavioral therapy (CBT) being a standard treatment in major depressive disorder (MDD), nearly half of patients do not respond. As one of the predictors of CBT's efficacy is amygdala reactivity to positive information, which is often decreased in MDD, we explored whether real-time fMRI neurofeedback (rtfMRI-nf) training to increase amygdala responses during positive memory recall prior CBT would enhance its efficacy.
Real-Time Functional Magnetic Resonance Imaging Amygdala Neurofeedback Changes Positive Information Processing in Major Depressive Disorder. [2019]In participants with major depressive disorder who are trained to upregulate their amygdalar hemodynamic responses during positive autobiographical memory recall with real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. This study tested whether amygdalar rtfMRI-nf also changes emotional processing of positive and negative stimuli in a variety of behavioral and imaging tasks.
Connectivity based Real-Time fMRI Neurofeedback Training in Youth with a History of Major Depressive Disorder. [2023]Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) has proven to be a powerful technique to help subjects to gauge and enhance emotional control. Traditionally, rtfMRI-nf has focused on emotional regulation through self-regulation of amygdala. Recently, rtfMRI studies have observed that regulation of a target brain region is accompanied by connectivity changes beyond the target region. Therefore, the aim of present study is to investigate the use of connectivity between amygdala and prefrontal regions as the target of neurofeedback training in healthy individuals and subjects with a life-time history of major depressive disorder (MDD) performing an emotion regulation task.
Self-regulation of amygdala activation using real-time FMRI neurofeedback. [2021]Real-time functional magnetic resonance imaging (rtfMRI) with neurofeedback allows investigation of human brain neuroplastic changes that arise as subjects learn to modulate neurophysiological function using real-time feedback regarding their own hemodynamic responses to stimuli. We investigated the feasibility of training healthy humans to self-regulate the hemodynamic activity of the amygdala, which plays major roles in emotional processing. Participants in the experimental group were provided with ongoing information about the blood oxygen level dependent (BOLD) activity in the left amygdala (LA) and were instructed to raise the BOLD rtfMRI signal by contemplating positive autobiographical memories. A control group was assigned the same task but was instead provided with sham feedback from the left horizontal segment of the intraparietal sulcus (HIPS) region. In the LA, we found a significant BOLD signal increase due to rtfMRI neurofeedback training in the experimental group versus the control group. This effect persisted during the Transfer run without neurofeedback. For the individual subjects in the experimental group the training effect on the LA BOLD activity correlated inversely with scores on the Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale. The whole brain data analysis revealed significant differences for Happy Memories versus Rest condition between the experimental and control groups. Functional connectivity analysis of the amygdala network revealed significant widespread correlations in a fronto-temporo-limbic network. Additionally, we identified six regions--right medial frontal polar cortex, bilateral dorsomedial prefrontal cortex, left anterior cingulate cortex, and bilateral superior frontal gyrus--where the functional connectivity with the LA increased significantly across the rtfMRI neurofeedback runs and the Transfer run. The findings demonstrate that healthy subjects can learn to regulate their amygdala activation using rtfMRI neurofeedback, suggesting possible applications of rtfMRI neurofeedback training in the treatment of patients with neuropsychiatric disorders.
Resting-state functional connectivity modulation and sustained changes after real-time functional magnetic resonance imaging neurofeedback training in depression. [2022]Amygdala hemodynamic responses to positive stimuli are attenuated in major depressive disorder (MDD) and normalize with remission. Real-time functional magnetic resonance imaging neurofeedback (rtfMRI-nf) training with the goal of upregulating amygdala activity during recall of happy autobiographical memories (AMs) has been suggested, and recently explored, as a novel therapeutic approach that resulted in improvement in self-reported mood in depressed subjects. In this study, we assessed the possibility of sustained brain changes as well as the neuromodulatory effects of rtfMRI-nf training of the amygdala during recall of positive AMs in MDD and matched healthy subjects. MDD and healthy subjects went through one visit of rtfMRI-nf training. Subjects were assigned to receive active neurofeedback from the left amygdale (LA) or from a control region putatively not modulated by AM recall or emotion regulation, that is, the left horizontal segment of the intraparietal sulcus. To assess lasting effects of neurofeedback in MDD, the resting-state functional connectivity before and after rtfMRI-nf in 27 depressed subjects, as well as in 27 matched healthy subjects before rtfMRI-nf was measured. Results show that abnormal hypo-connectivity with LA in MDD is reversed after rtfMRI-nf training by recalling positive AMs. Although such neuromodulatory changes are observed in both MDD groups receiving feedback from respective active and control brain regions, only in the active group are larger decreases of depression severity associated with larger increases of amygdala connectivity and a significant, positive correlation is found between the connectivity changes and the days after neurofeedback. In addition, active neurofeedback training of the amygdala enhances connectivity with temporal cortical regions, including the hippocampus. These results demonstrate lasting brain changes induced by amygdala rtfMRI-nf training and suggest the importance of reinforcement learning in rehabilitating emotion regulation in depression.
Real-time neurofeedback using functional MRI could improve down-regulation of amygdala activity during emotional stimulation: a proof-of-concept study. [2021]The amygdala is a central target of emotion regulation. It is overactive and dysregulated in affective and anxiety disorders and amygdala activity normalizes with successful therapy of the symptoms. However, a considerable percentage of patients do not reach remission within acceptable duration of treatment. The amygdala could therefore represent a promising target for real-time functional magnetic resonance imaging (rtfMRI) neurofeedback. rtfMRI neurofeedback directly improves the voluntary regulation of localized brain activity. At present, most rtfMRI neurofeedback studies have trained participants to increase activity of a target, i.e. up-regulation. However, in the case of the amygdala, down-regulation is supposedly more clinically relevant. Therefore, we developed a task that trained participants to down-regulate activity of the right amygdala while being confronted with amygdala stimulation, i.e. negative emotional faces. The activity in the functionally-defined region was used as online visual feedback in six healthy subjects instructed to minimize this signal using reality checking as emotion regulation strategy. Over a period of four training sessions, participants significantly increased down-regulation of the right amygdala compared to a passive viewing condition to control for habilitation effects. This result supports the concept of using rtfMRI neurofeedback training to control brain activity during relevant stimulation, specifically in the case of emotion, and has implications towards clinical treatment of emotional disorders.
Down-regulation of amygdala activation with real-time fMRI neurofeedback in a healthy female sample. [2021]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.
fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity. [2017]Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: p
Amygdala real-time functional magnetic resonance imaging neurofeedback for major depressive disorder: A review. [2020]Advances in imaging technologies have allowed for the analysis of functional magnetic resonance imaging data in real-time (rtfMRI), leading to the development of neurofeedback (nf) training. This rtfMRI-nf training utilizes functional magnetic resonance imaging (fMRI) tomographic localization capacity to allow a person to see and regulate the localized hemodynamic signal from his or her own brain. In this review, we summarize the results of several studies that have developed and applied neurofeedback training to healthy and depressed individuals with the amygdala as the neurofeedback target and the goal to increase the hemodynamic response during positive autobiographical memory recall. We review these studies and highlight some of the challenges and advances in developing an rtfMRI-nf paradigm for broader use in psychiatric populations. The work described focuses on our line of research aiming to develop the rtfMRI-nf into an intervention, and includes a discussion of the selection of a region of interest for feedback, selecting a control condition, behavioral and cognitive effects of training, and predicting which participants are most likely to respond well to training. While the results of these studies are encouraging and suggest the clinical potential of amygdala rtfMRI-nf in alleviating symptoms of major depressive disorder, larger studies are warranted to confirm its efficacy.
Clinical Application of Real-Time fMRI-Based Neurofeedback for Depression. [2021]Real-time functional magnetic resonance imaging-based neurofeedback (rt-fMRI NF) is a recent technique used to train self-regulation of circumscribed brain areas or networks. For clinical applications in depression, NF training targets brain areas with disturbed activation patterns, such as heightened reactivity of amygdala in response to negative stimuli, in order to normalize the neurophysiology and their behavioral correlates. Recent studies have targeted emotion processing areas such as the amygdala, the salience network, and top-down control areas such as the lateral prefrontal cortex. Different methods of rt-fMRI-based NF in depression, their potential for clinical improvement, and most recent advancements of this technology are discussed considering their role for future clinical applications. Initial findings of randomized controlled trials show promising results. However, for lasting treatment effects, clinical efficiency and optimal target regions, tasks, control conditions, and duration of training need to be established.