Characterization of the Relationship Between the Mesolimbic Reward System and Immune Functioning in Humans Via fMRI Neurofeedback

Characterization of the Relationship Between the Human Mesolimbic Reward System and Immune Functioning


Lead sponsor: Tel-Aviv Sourasky Medical Center

Collaborator: Technion, Israel Institute of Technology

Source Tel-Aviv Sourasky Medical Center
Brief Summary

The purpose of this study is to characterize the link between neurobehavioral measures of the mesolimbic reward system and immune functioning in healthy individuals, via fMRI neurofeedback modulation of mesolimbic reward system, and the consecutive assesment of immune response to Hepatitis B vaccination.

Detailed Description

For many years, the link between mental processes and physical health has remained obscure. Yet, over time, studies have begun to shed light on the intimate relationship between one's physical condition and mental state. One body of research aimed at elucidating the mind-body relationship is the study of the placebo effect. Placebo effects result mainly from conscious expectations to become healthy in therapeutic settings, and from unconscious conditioned responses to therapeutical settings that predict beneficial outcomes. Both processes are asociated with the neuronal reward system, which mediates reward processing, reward valuation and value based-learning. However, it remains unclear how do these processes mediated by the reward system promote therapeutic effects?

A recent study established a causal relationship between mesolimbic activation (VTA) and a measurable immunological response in mice. Stimulation of the VTA increased anti-bacterial immune functioning, an effect that was mediated by sympathetic nervous system, which is regulated by the brain and innervates all immune organs.

In light of these findings, the current study aims to assess the relationship between reward-related brain activation and immune functions in humans. fMRI Neurofeedback, a task that allows individuals to self modulate specified neural patterns in real-time, will be used to induce mesolimbic activation, following which healthy individuals will vaccinate against Hepatitis B. Immunological effects will be assessed by comparing immunological measures with respect to Hepatitis B prior and following mesolimbic activation and Hepatitis B vaccination.

The long-term goal of this study is to demonstrate a causal link between reward activation and an objective measurable physiological response of great significance, and to develop the means for individuals to exploit such mechanism for boosting immune functioning. i.e. to harness endogenous reward-related brain activation to strengthen the immune system, for clinical pathologies such as autoimmune diseases, maleble pathogens, cancer, etc.

Overall Status Recruiting
Start Date January 20, 2019
Completion Date March 28, 2022
Primary Completion Date December 31, 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Immunological: change in anti HBs immunoglobins in plasma 6 weeks
Immunological: change in cytokines blood concentrations following vaccination 10-24 days
fMRI Neurofeedback task modulation success 1-3 weeks
Secondary Outcome
Measure Time Frame
Neurobehavioral measures of reward anticipation and responsivity during Monetary Incentive Delay (MID) task. 6 weeks
Behavioral measures of incentive motivation extracted from Effort Expenditure for Rewards Task (EEfRT). 6 weeks
Motivational tendencies based on K-means cluster analysis of questionnaires scores 6 week
Functional connectivity of mesolimbic network during rest fMRI scan 1-3 weeks
long term immunological effects 3 months
Subjective reports of SHAPS (Snaith-Hamilton Pleasure Scale) 6 weeks
Subjective reports to Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) 6 weeks
Subjective reports to Tridimensional Personality Questionnaire (TPQ) 6 weeks
Enrollment 87

Intervention type: Behavioral

Intervention name: Neuromodulation via fMRI Neurofeedback task

Description: Two active neurofeedback groups will practice to up regulate their designated neural targets via identical experimental protocol (varying only the origin of the feedback).

Intervention type: Biological

Intervention name: Hepatitis B vaccination

Description: Subjects will be vaccinated against Hepatitis B



Inclusion Criteria:

- Healthy participants

- Normal or corrected to normal vision

- Compatibility with general MRI requirements

Exclusion Criteria:

- History of neurological or psychiatric diseases

- Have received Hepatitis B vaccination in the last 10 years

Gender: All

Minimum age: 18 Years

Maximum age: 60 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Talma Hendler, MD, PhD Principal Investigator Tel-Aviv Sourasky Medical Center
Overall Contact

Last name: Nitzan Lubianiker

Phone: 972-5033334538

Email: [email protected]

facility status contact Functional Brain Center, Sourasky Medical Center Talma Hendler, MD, PhD 972-36973953 [email protected]
Location Countries


Verification Date

February 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: Mesolimbic Neurofeedback

Arm group type: Experimental

Description: Neuromodulation via fMRI Neurofeedback task: subjects will participate in four fMRI-NF sessions, up-regulating co-activation of three mesolimbic reward nodes: ventral tegmental area, and bilateral ventral striatum. Hepatitis B vaccination: subjects will receive vaccination against Hepatitis B.

Arm group label: Control Neurofeedback

Arm group type: Active Comparator

Description: Neuromodulation via fMRI Neurofeedback task: subjects will participate in four fMRI-NF sessions, up-regulating co-activation of regions comprising with one of K control networks. Hepatitis B vaccination: subjects will receive vaccination against Hepatitis B.

Arm group label: Natural history

Arm group type: Other

Description: No brain manipulation (Assesment of natural history immune response). Hepatitis B vaccination: subjects will receive vaccination against Hepatitis B.

Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: Experimental arm: fMRI neurofeedback to mesolimbic system (the ventral tegmental area, and bilateral ventral striatum).
Active control arm: fMRI neurofeedback to a control network.
Natural history arm: assessment of immunological response to Hepatitis B without neurofeedback manipulation.

Primary purpose: Basic Science

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Masking description: Both participants and study personnel (Investigators and outcomes assessor) in the two active experimental arms (Mesolimbic NF and Control NF) will be blinded to group allocation.