MRI Neurofeedback for Enhancing Motivation

Overseen By R. Alison Adock, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Psychiatric medications

Disqualifiers: Neurological disorders, Serious medical illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how individuals can control their motivation by observing brain activity through MRI scans. Participants will perform tasks that activate brain areas linked to motivation, potentially enhancing memory and decision-making. The trial uses a technique called Ventral tegmental area of dopaminergic midbrain (VTA) fMRI neurofeedback, allowing participants to view and possibly influence their brain activity. The trial seeks healthy, right-handed individuals who have not experienced significant mental health issues or serious medical conditions in the past six months. Participants must feel comfortable in an MRI machine. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on brain motivation control.

Will I have to stop taking my current medications?

The trial excludes people who have used prescription medications for psychiatric conditions in the past six months, so if you're taking such medications, you may not be eligible to participate.

What prior data suggests that this MRI neurofeedback technique is safe?

Research shows that targeting a specific area in the brain using brain imaging is generally safe. Early studies found that this method is well-tolerated, with only minor side effects, suggesting it does not pose significant risks. The goal is to help people learn to better control their motivation. Other research has used this approach, further supporting its safety for participants. While the treatment remains under study, the evidence so far supports its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial exploring MRI neurofeedback targeting the ventral tegmental area (VTA) of the dopaminergic midbrain because it's a novel way to boost motivation. Unlike traditional treatments that might involve medication or cognitive-behavioral approaches, this method uses real-time brain imaging to help participants actively engage and enhance their brain's motivation centers. This technique aims to empower individuals to stimulate their own motivation through personal thoughts and imagery, potentially offering a more direct and immediate impact on motivation-related challenges. The trial hopes to uncover whether this approach can effectively enhance motivated memory and decision-making, offering a new tool for improving motivation without relying on medication.

What evidence suggests that this neurofeedback technique is effective for enhancing motivation?

Previous studies have found that using neurofeedback to target the ventral tegmental area (VTA) of the brain helps people learn to boost their own motivation. This area plays a crucial role in motivation and the sensation of reward. One study showed that participants who received real-time feedback during MRI sessions could activate their VTA more effectively. Another study confirmed that this feedback method significantly increased VTA activity. In this trial, participants will engage in different arms to explore the effects of VTA fMRI neurofeedback on motivation. These findings suggest that VTA fMRI neurofeedback might be a promising way to enhance motivation by helping individuals control their brain activity. ^{4 6 7 8 9}

Who Is on the Research Team?

R. Alison Adock, MD, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for healthy right-handed individuals aged 18-45 who use effective birth control if of childbearing capacity. It's not suitable for those with psychiatric medication use in the past six months, serious medical conditions, certain neurological disorders, metal implants, claustrophobia, or a weight over 250 pounds.

Inclusion Criteria

I am either male or female.

Right-handed

I am in good overall health.

Exclusion Criteria

I have been on medication for a mental health condition in the past 6 months.

I do not have major neurological disorders or conditions that prevent MRI use.

I have had a head injury that made me lose consciousness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline and Memory Encoding

Participants undergo baseline assessments and memory encoding tasks

1 week

1 visit (in-person)

Memory Retrieval and Encoding

Participants complete memory retrieval and encoding tasks, 24 hours apart

1 week

2 visits (in-person)

Effort-Based Decision Making

Participants complete effort-based learning tasks and questionnaires

1 week

2 visits (in-person)

Follow-up

Participants are monitored for changes in effort-based decision making and motivated memory

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ventral tegmental area of dopaminergic midbrain (VTA) fMRI neurofeedback

Trial Overview The study aims to understand self-regulation of motivation by providing participants with real-time feedback on their brain activity using MRI technology focused on a specific area related to dopamine production.

How Is the Trial Designed?

Group I: Intentional Versus Cue-Evoked Midbrain Activation Experimental Treatment 1 Intervention

Participants meeting study inclusion will be scheduled for two sessions: one baseline behavioral visit and an fMRI session to assess the ability to self-stimulate VTA activation. Session one will include a battery of cognitive assessments and a demonstration of the reward-based learning task in session two. The experimental imaging task session will be done within one week of session one. Participants will been randomly split into two group: group one will complete a reward-based learning task before the VTA activation task and group two will complete reward task after VTA activation. During the VTA activation task, participants will be instructed to achieve a heightened state of motivation using personally relevant thoughts and imagery.

Group II: Intentional Midbrain Activation Effects on Motivated Memory Experimental Treatment 1 Intervention

Participants will take part in four sessions: visit 1-baseline + memory encoding, visit 2-memory retrieval, visit 3-memory encoding, visit 4-memory retrieval). Encoding and retrieval of the memoranda will occur 24 hours apart. Study visits will take place no more than 7 days apart. One group of participants will complete all sessions at the Center for Cognitive Neuroscience. The remainder of participants will complete the encoding sessions in the MRI machine, .

Group III: Intentional Midbrain Activation Effects on Effort-Based Decision Making Experimental Treatment 1 Intervention

Participants will be randomly assigned to an MRI group or a behavioral control group. All participants will complete an effort-based learning task and a series of questionnaires in session one. Session two may include an MRI based on group assignment. Participants in the MRI group will complete the VTA activation task. Following, they will complete the effort task and questionnaires a second time. The behavioral control group will complete a second session consisting of the effort task and questionnaires.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Healthy volunteers can successfully increase activity in the left premotor cortex (PMC) during a motor imagery task using fMRI neurofeedback, indicating the potential for self-regulation of brain activity.

The neurofeedback group not only enhanced PMC activity but also showed increased activation in other motor control regions, suggesting that this technique could be beneficial for rehabilitation in conditions like stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex. Marins, TF., Rodrigues, EC., Engel, A., et al.[2020]

Participants who underwent real-time VTA neurofeedback training were able to voluntarily activate the ventral tegmental area (VTA) without external aids, indicating a new method to enhance motivation and learning.

This self-activation of the VTA was linked to increased connectivity in the mesolimbic network, suggesting that neurofeedback training can lead to lasting changes in brain function related to motivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Neurostimulation: Learning to Volitionally Sustain Ventral Tegmental Area Activation. MacInnes, JJ., Dickerson, KC., Chen, NK., et al.[2019]

Individuals can voluntarily activate the dopaminergic system in the substantia nigra/ventral tegmental area (SN/VTA) using mental imagery, with real-time feedback enhancing this ability.

Participants receiving direct feedback on their SN/VTA activity were better able to increase this activity compared to those receiving inverted feedback, suggesting that neurofeedback can improve self-regulation of dopamine release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback-mediated self-regulation of the dopaminergic midbrain. Sulzer, J., Sitaram, R., Blefari, ML., et al.[2021]

In a study involving 24 healthy participants, 74% of those trained to self-regulate their nucleus accumbens (NAcc) using real-time fMRI neurofeedback successfully learned to do so, leading to improved motivation in cognitive tasks.

Participants who effectively self-regulated their NAcc showed changes in brain connectivity related to reward processing, while the control group did not experience these benefits, highlighting the potential of neurofeedback as a novel intervention for motivation-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving motivation through real-time fMRI-based self-regulation of the nucleus accumbens. Li, Z., Zhang, CY., Huang, J., et al.[2019]

A randomized controlled trial involving 31 boys with ADHD demonstrated that real-time functional magnetic resonance neurofeedback (rtfMRI-NF) targeting the right inferior prefrontal cortex (rIFG) significantly reduced ADHD symptoms and improved cognitive function over a follow-up period of 11 months.

The study found that only the rIFG group showed a transfer effect to everyday life, correlating with symptom reductions and increased activation in the rIFG during tasks requiring inhibition, highlighting the potential of rtfMRI-NF as a targeted intervention for ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder. Alegria, AA., Wulff, M., Brinson, H., et al.[2018]

The study involving 59 participants found that successful self-regulation of dopaminergic midbrain activity through neurofeedback is linked to individual differences in prefrontal reward sensitivity, suggesting that reinforcement learning plays a key role in this process.

Increased activity in cognitive control areas during the transfer phase (when feedback is no longer available) indicates that effective self-regulation may rely on the ability to manage cognitive processes, which could help in tailoring neurofeedback training for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of individual differences in neurofeedback training illuminates successful self-regulation of the dopaminergic midbrain. Hellrung, L., Kirschner, M., Sulzer, J., et al.[2022]

In a study using fMRI-based neurofeedback, participants were able to increase their own activity in the nucleus accumbens (NAcc), a brain region important for motivation and learning, especially when provided with real-time feedback.

The ability to control NAcc activity was linked to positive emotional arousal, suggesting that neurofeedback could be a potential therapeutic tool for enhancing motivation and learning, although participants struggled to decrease NAcc activity and the control did not last after feedback was removed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Control of nucleus accumbens activity with neurofeedback. Greer, SM., Trujillo, AJ., Glover, GH., et al.[2021]

In a double-blind, sham-controlled trial involving 88 boys with ADHD, fMRI neurofeedback targeting the right inferior frontal cortex did not show significant improvements in ADHD symptoms compared to a sham treatment, indicating it may not be an effective intervention.

Both groups experienced similar reductions in symptoms, with the sham group even showing greater improvements in irritability and motor inhibition, suggesting that the active fMRI-NF did not provide the expected benefits and had no significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-Blind, Sham-Controlled Randomized Trial Testing the Efficacy of fMRI Neurofeedback on Clinical and Cognitive Measures in Children With ADHD. Lam, SL., Criaud, M., Lukito, S., et al.[2023]

Citations

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Learning to Volitionally Sustain Ventral Tegmental Area ... Using fMRI, we found untrained participants' motivational strategies failed to consistently activate VTA. After real-time VTA neurofeedback ...

2. 2018.ccneuro.org 2018.ccneuro.org/proceedings/1204.pdf

Temporal structure of learning to regulate ventral tegmental ... The ventral tegmental area (VTA) and its dopaminergic projections are central to volitional behavior. Previous research from our group demonstrated that ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26948894/

Learning to Volitionally Sustain Ventral Tegmental Area ... Using fMRI, we found untrained participants' motivational strategies failed to consistently activate VTA. After real-time VTA neurofeedback ...

4. cell.com cell.com/cms/10.1016/j.neuron.2016.02.002/attachment/ddbc338c-f251-404b-b648-41e7e6bd64a1/mmc1.pdf

Cognitive Neurostimulation Training: The VTA Feedback group significantly activated the VTA above baseline during the early phase of the trial (P < 0.0005). The NAcc Feedback group ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9391365/

Analysis of individual differences in neurofeedback training ... Analysis of real-time fMRI data from 59 participants undergoing neurofeedback training suggests that reinforcement learning contributes to successful self- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10732355/

A feasibility study of goal-directed network-based real-time ... The rt-fMRI NF training may have clinical implications with improved safety and minor side effects (31). Methods and analysis. Aim. To determine whether rt-fMRI ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9947361/

Neurofeedback-dependent influence of the ventral striatum ... This study reinforces DLPFC as a robust target for neurofeedback clinical implementations and enhances the critical influence of the ventral striatum.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1053811923003348

Development and validation of an fMRI-informed EEG ... We developed and validated a scalable, fMRI-informed EEG model for monitoring reward processing related to activation in the ventral-striatum (VS).

9. sciencedirect.com sciencedirect.com/science/article/pii/S2352853225000550

Functional magnetic resonance imaging in adolescent ... fMRI research provides a neuroimaging foundation for the objective diagnosis and targeted intervention of IGD. Future research necessitates the ...