Pulsed tVNS Protocol and Reinforcement Learning

NCT06205108 | Unknown

• 1 other identifier: BON002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to investigate the potential of a phasic taVNS stimulation protocol for reinforcement learning. The investigators will disentangle its effects on learning actions and outcomes through the administration of pulsed stimulation during different stages of learning (stimulation during action vs. stimulation during outcome). This will provide insights into optimal stimulation timing and help determine whether pulsed vagal stimulation can be more effective when paired with instrumental actions or rewarding feedback. Developing a tool that non-invasively improves value-based decision-making by using pulsed stimulation would redefine the application options of taVNS. It will enable tVNS to act as a teaching signal comparable to physiological signals in reward-based learning. In the long run, this may inform targeted interventions for individuals with altered reward function, a key symptom in a range of mental disorders. As part of the study, The investigators will test three hypotheses: H1 - Instrument Learning Task: Participants will show improved action-outcome learning when positive feedback after a cue is paired with an effective high-intensity stimulation compared to sham stimulation (sham/taVNS). H2 - Instrumental Learning Task: Participants will show improved action-outcome learning when the action leading to a reward with higher probability (i.e., correct choice) is stimulated with high intensity stimulation. Again, this will only be observable for active but not sham stimulation (sham/taVNS). H3 - Functional Magnetic Resonance Imaging (fMRI): Behavioral gains in learning of the cues in the high-intensity active stimulation condition are correlated with higher signals in the midbrain and dorsal striatum during feedback (reward presentation) or action.

Conditions

Vagus Nerve Stimulation in Reward Learning

Outcome Measures

Primary Outcomes (6)

• Choice accuracy

  Quantified by the accuracy of action upon cue presentation during the Reinforcement Learning Task. Between-condition, within-subject effects (taVNS vs. Sham stimulation). Stimulation order and stimulation intensity will be used as covariates.

  1 hour

• Response times

  Time taken by a participant to perform an action after cue presentation. Stimulation order and stimulation intensity will be used as covariates.

  1 hour

• Learning rate from a reinforcement learning model

  Individual choices will be used to derive individual learning rates by modeling reinforcement learning using Q-learning. We will perform model comparisons (WAIC) to determine whether separate learning rates for tVNS and sham explain the data better. Additionally, we will use model comparisons to assess whether modulations of the learning rate taVNS specifically during action, feedback, or both will explain the data better. Moreover, we will use bootstrapping to compare learning rates between conditions (sham vs. tVNS). We will use Bayesian Hierarchical Modeling (STAN) for model estimation and model comparisons (WAIC). Stimulation order and stimulation intensity will be used as covariates.

  1 hour

• Reward sensitivity from reinforcement learning model

  Individual choices will be used to derive the individual reward sensitivities by modeling reinforcement learning using Q-learning. We will perform model comparisons (WAIC) to determine whether separate reward sensitivities for tVNS and sham explain the data better. Additionally, we will use model comparisons to assess whether modulations of the reward sensitivity by taVNS specifically during action, feedback, or both will explain the data better. Moreover, we will use bootstrapping to compare reward sensitivities between conditions (sham vs. tVNS). We will use Bayesian Hierarchical Modeling (STAN) for model estimation and model comparisons (WAIC). Stimulation order and stimulation intensity will be used as covariates.

  1 hour

• Changes in brain response during cue presentation

  taVNS-induced changes reward-related brain activity (3T). We will assess changes (tVNS vs. sham, full factorial in SPM) in during cue anticipation. We will assess changes in a mask including the striatum and midbrain defined with the Harvard Oxford Atlas including an improved midbrain.

  1 hour

• Changes in brain response associated with reward prediction errors

  taVNS-induced changes reward-related brain activity (3T). We will compare changes (tVNS vs. sham, full factorial in SPM) in the model-based fMRI contrasts representing reward prediction errors at feedback presentation. Since behavioral changes in model parameters affect model-based regressors, they may introduce changes unrelated to neural effects. We will first compare models (BIC) to determine whether individual-level parameters or group-level parameters explain the neural data better. We then test taVNS-induced changes in the winning model and report changes in the other one as sensitivity analyses. We will assess correlated brain activation in a mask including the striatum and midbrain defined with the Harvard Oxford Atlas including an improved midbrain.

  1 hour

Secondary Outcomes (3)

• Stimulation intensity

  2 minutes post stimulation

• Changes in brain response win vs. loss

  1 hour

• Changes in brain response associated with expected value during cue presentation

  1 hour

Study Arms (2)

taVNS stimulation

EXPERIMENTAL

taVNS is a non-invasive technique to stimulate the auricular branch of the vagus nerve. Transcutaneous electrodes are placed in the cymba concha of the ear and short bursts (20Hz, 1s, 400µs pulse widths) of stimulation are delivered either in parallel to the action or the feedback. Stimulation strength is individually calibrated. Stimulation lasts \~1h in the session.

Device: taVNS stimulation

sham stimulation

SHAM COMPARATOR

Stimulation at the earlobe that is not innervated by the vagus nerve with the same parameters (short bursts, 20Hz, 1s, 400µs pulse widths, delivered in parallel to the action or the feedback). Stimulation strength is individually calibrated. Stimulation lasts \~1h throughout the study. Stimulation lasts \~1h in the session.

Device: sham stimulation

Interventions

taVNS stimulation DEVICE

Non-invasive stimulation of the auricular branch of the vagus nerve (cymba conchae). Research device from tVNS technologies.

taVNS stimulation

sham stimulation DEVICE

Non-invasive stimulation of the ear lob (not innervated by the vagus nerve). Research device from tVNS technologies.

sham stimulation

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 35
• Body-Mass-Index between 18.5 and 30.0 kg/m2
• Providing written informed consent
• Normal or corrected-to-normal vision

You may not qualify if:

• acute:
• skin lesions at the stimulation site (e.g., wounds, inflammation),
• earrings or piercings on the left or right ear which cannot be removed,
• implants (pacemaker, cochlear implant, cerebral shunt),
• required permanent use of hearing aid,
• pregnant or nursing,
• other contraindications for MRI (e.g. claustrophobia) lifetime:
• brain injury,
• schizophrenia,
• bipolar disorder,
• severe substance use disorders,
• coronary heart disease,
• stroke,
• diabetes,
• epilepsy,

Sponsors & Collaborators

• University of Bonn: lead

Study Sites (1)

Section of Medical Psychology, University Hospital Bonn

Bonn, Germany

RECRUITING

Central Study Contacts

Nils B Kroemer, Dr.

CONTACT

49 228 287-19123; nkroemer@uni-bonn.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medical Psychology

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: January 12, 2024
• Study Start: November 28, 2023
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: January 12, 2024

Record last verified: 2024-01

Locations

DE (1)