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

Tel Aviv Sourasky Medical Center

Status: Completed

Conditions: Immune Hepatitis

Treatments: Biological: Hepatitis B vaccination; Behavioral: Neuromodulation via fMRI Neurofeedback task

Study type: Interventional

Funder types: Other

Identifiers

NCT03951870

0664-17-TLV

Details and patient eligibility

About

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.

Full 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.

Enrollment: 85 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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85 participants in 3 patient groups

Mesolimbic Neurofeedback

Experimental group

Description:

Neuromodulation via fMRI Neurofeedback task: subjects (n=34) will participate in four fMRI-NF sessions, up-regulating activation of three mesolimbic reward nodes: ventral tegmental area, and bilateral ventral striatum. ROIs are 5 mm spheres around peak activations in funcitonal localizer task (Monetary Incentive delay, reward anticipation contrast), within a predifned meta-analytic anatomical masks of the three regions. anatomical masks: VTA (Midbrain): -4 -24 -10 \*see below Right Nac: 12 10 -4 Left Nac: -10 10 -6 Oldham, Stuart, et al. Human brain mapping (2018). \* 23/08/22: Due to VTA complex contours, it was not restricted according to Oldham et al as mentioned above, but via more accurate VTA mask (Murty et al. 2014, NeuroImage). This was mistakenly left out of the original preregistration. It is noteworthy that, to date (23/8/22), ROI analyses haven't been performed. Hepatitis B vaccination: subjects will receive vaccination against Hepatitis B.

Treatment:

Biological: Hepatitis B vaccination

Behavioral: Neuromodulation via fMRI Neurofeedback task

Control Neurofeedback

Active Comparator group

Description:

Neuromodulation via fMRI Neurofeedback task: subjects (n=34) will participate in four fMRI-NF sessions, up-regulating activation of regions comprising one of 4 control networks (5mm spheres around MNI coordinates): Motor Imagery (Hétu, Sébastien, et al. Neurosci. \& Biobehav Rev (2013)) R. Cerebellum: 32 -62 -28 L. Cerebellum: -32 -56 -30 L. Precentral Gyrus: -26 -2 58; Auditory imagery (McNorgan, Chris.Front in Human Neurosci 6 (2012)) R STG:64 -30 9 L IFG:-48 24 -5 L precentral Gyrus: -52 1 47; Arithmetic processing (Arsalidou, Marie, and Margot J. Taylor. Nuroimage (2011)) R. SPL: 29 -66 49 L. MFG (dlpfc): -45 32 29 L. precuneus: -28 -71 33; Spatial Navigation (Kühn, Simone, and Jürgen Gallinat. Human Brain Map. (2014)) R. hippocampus 26 -35 -11 L. hippocampus -26 -47 -9 L. Post. cingulate -15 -59 19 Hepatitis B vaccination: subjects will receive vaccination against Hepatitis B.

Treatment:

Biological: Hepatitis B vaccination

Behavioral: Neuromodulation via fMRI Neurofeedback task

Natural history

Other group

Description:

No brain manipulation (Assesment of natural history immune response). Hepatitis B vaccination: subjects (n=17) will receive vaccination against Hepatitis B.

Treatment:

Biological: Hepatitis B vaccination