Clinical trial NCT03951870: Characterization of the Relationship Between the Human Mesolimbic Reward System and Immune Functioning
Official title: Characterization of the Relationship Between the Mesolimbic Reward System and Immune Functioning in Humans Via fMRI Neurofeedback
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Immune Hepatitis
Keywords: mesolimbic reward system
fMRI Neurofeedback
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Technion, Israel Institute of Technology
First posted: 2019-05-15
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. Experimental arm: fMRI neurofeedback to mesolimbic system (the ventral tegmental area, and bilateral ventral striatum).
2. Active control arm: fMRI neurofeedback to a control network.
3. Natural history arm: assessment of immunological response to Hepatitis B without neurofeedback manipulation.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* Healthy participants
* Normal or corrected to normal vision
* Compatibility with general MRI requirements

Exclusion Criteria:

* History of neurological or psychiatric diseases that lead to hospitalization
* Have received Hepatitis B vaccination in the last 10 years
* Memory/cognitive neurological impairments
* Chronic heart disease, diabities, high blood pressure, or autoimmune disease.

Primary outcomes:
measure: Immunological: change in anti HBs immunoglobins in plasma
timeFrame: 6 weeks
measure: Immunological: change in cytokines blood concentrations following vaccination
timeFrame: 17 days
measure: Reward Mesolimbic network (or control networks) BOLD activity during fMRI-NF task
timeFrame: 1-3 weeks
Secondary outcomes:
measure: Mental Strategies Questionnaire for NeuroFeedback (MSQ-NF)
timeFrame: 6 weeks
measure: Neurobehavioral measures of reward anticipation and responsivity during Monetary Incentive Delay (MID) task.
timeFrame: 6 weeks
measure: Behavioral measures of incentive motivation extracted from Effort Expenditure for Rewards Task (EEfRT).
timeFrame: 6 weeks
measure: Motivational tendencies based on K-means cluster analysis of questionnaires scores
timeFrame: 6 week
measure: Functional connectivity of mesolimbic network during rest fMRI scan
timeFrame: 1-3 weeks
measure: long term immunological effects
timeFrame: 3 months
measure: Subjective reports of SHAPS (Snaith-Hamilton Pleasure Scale)
timeFrame: 6 weeks
measure: Subjective reports to Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ)
timeFrame: 6 weeks
measure: Subjective reports to Tridimensional Personality Questionnaire (TPQ)
timeFrame: 6 weeks
measure: Autonomic Nervous System (ANS) measure: Heart Rate Variability (HRV)
timeFrame: 3 days - 4 weeks
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Functional Brain Center, Sourasky Medical Center
Study officials:
affiliation: Tel-Aviv Sourasky Medical Center
name: Talma Hendler, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: