Longitudinal Effects of Brain Stimulation on Decision-Making and Reward Learning

NCT07823218 | Not Yet Recruiting

• 1 other identifier: BON009
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the longitudinal effects of brain stimulation treatments on decision-making and reward learning. Here, we use daily assessments of reinforcement learning behavior in patients with depression who receive neuromodulation treatment to study potential associations between changes in decision-making and reward learning and changes in clinical symptoms.

Conditions

Depression / Major Depressive Disorder

Keywords

Brain Stimulation; Reinforcement Learning; ECT; repetitive transcranial magnetic stimulation; VNS; tVNS; Depression

Outcome Measures

Primary Outcomes (1)

• Punishment learning rates

  The primary outcome are punishment learning rate estimates from a computational reinforcement learning model. Learning rates will be compared within and between stimulation conditions. Reinforcement learning is repeatedly measured with a bandit task with fluctuating reward probabilities (reward learning task). Reward learning behavior will be collected online over up to 60 runs, each including 150 trials.

  Assessed online up to 5 times before the first stimulation treatment and daily throughout the study (8 weeks).

Secondary Outcomes (17)

• Stimulation-induced mid-term changes in the backward digit span

  Assessed before the first stimulation treatment and after 4 and 8 weeks (10 minutes).

• Correct choices in the reward learning task

  Assessed online at least 5 times before the first stimulation treatment and daily throughout the study (8 weeks).

• Reward sensitivity

  Assessed online at least 5 times before the first stimulation treatment and daily throughout the study (8 weeks).

• Weighting of learned values and rewards at stake (lambda)

  Assessed online at least 5 times before the first stimulation treatment and daily throughout the study (8 weeks).

• Stimulation-induced mid-term changes in reward learning rates

  Assessed online at least 5 times before the first stimulation treatment and daily throughout the study (8 weeks).

Other Outcomes (3)

• Mood state

  Assessed online at least 5 times before the first stimulation treatment and daily throughout the study (8 weeks).

• Metabolic state

  Assessed online at least 5 times before the first stimulation treatment and daily throughout the study (8 weeks).

• Motivational state

  Assessed online at least 5 times before the first stimulation treatment and daily throughout the study (8 weeks).

Study Arms (5)

Electroconvulsive therapy (ECT)

Participants receive ECT as a treatment within the clinic. ECT intentionally causes a generalized seizure by passing electrical currents through the brain under anesthesia. The treatment protocol (e.g., number of treatments) is independent of study participation and follows the doctor's orders. Participants are enrolled after the treatment indication is confirmed.

Transcranial magnetic stimulation (TMS)

Participants receive TMS as a treatment within the clinic. TMS is a non-invasive procedure in which a magnetic coil is used to induce electrical currents in the brain and thus influence cortex activity. The treatment protocol (e.g., number of treatments, type of TMS) is independent of study participation and follows the doctor's orders. Participants are enrolled after the treatment indication is confirmed.

invasive vagus nerve stimulation (VNS)

Participants receive VNS as a treatment within the clinic. VNS is a surgical treatment in which a stimulation device is implanted that sends electrical impulses to the vagus nerve. The treatment protocol (e.g., stimulation settings) is independent of study participation and follows the doctor's orders. Participants are enrolled after the treatment indication is confirmed.

transcutaneous vagus nerve stimulation (tVNS)

Participants receive tVNS as a treatment from the clinic for at home stimulation. To stimulate vagal afferents, the electrode will be placed at the cymba conchae of the right ear using a previously established conventional stimulation protocol (30s ON, 30s OFF; tVNS E device, tVNS Technologies GmbH, Erlangen, Germany). The stimulation can be applied for up to 4h per day and participants self-select stimulation time and duration based on the doctor's orders. Participants are enrolled after the treatment indication is confirmed.

Control

Participants receive an indication for a stimulation treatment within the clinic, but do not make use of it. Participants are included after treatment indication.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients in the Department of Psychiatry and Psychotherapy at the University Hospital Bonn, who receive an indication for a brain stimulation treatment (ECT, TMS, VNS, taVNS).

You may qualify if:

• Indication for a brain stimulation treatment (ECT, TMS, VNS, taVNS) in the Department of Psychiatry and Psychotherapy at the University Hospital Bonn
• Be able and willing to provide informed consent.

You may not qualify if:

• Non-German speakers
• Unclear ability to give consent to the study participation

Sponsors & Collaborators

• Dr. Nils B. Kroemer: lead
• Department of Psychiatry University of Bonn: collaborator

Study Sites (1)

Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn

Bonn, 53127, Germany

Location

Related Publications (16)

• Neuser MP, Kuhnel A, Krautlein F, Teckentrup V, Svaldi J, Kroemer NB. Reliability of gamified reinforcement learning in densely sampled longitudinal assessments. PLOS Digit Health. 2023 Sep 6;2(9):e0000330. doi: 10.1371/journal.pdig.0000330. eCollection 2023 Sep.

  PMID: 37672521 BACKGROUND

• Huys QJM, Browning M. A Computational View on the Nature of Reward and Value in Anhedonia. Curr Top Behav Neurosci. 2022;58:421-441. doi: 10.1007/7854_2021_290.

  PMID: 34935117 BACKGROUND

• Kuehnel A, Zietz J, Theuer JK, Neuser MP, Kroemer NB; Dense sampling of choices links high learning rates to obesity and low reward sensitivity to binge eating; medRxiv; 2025 Jun 20

  BACKGROUND

• Weber I, Niehaus H, Krause K, Molitor L, Peper M, Schmidt L, Hakel L, Timmermann L, Menzler K, Knake S, Oehrn CR. Trust your gut: vagal nerve stimulation in humans improves reinforcement learning. Brain Commun. 2021 Mar 14;3(2):fcab039. doi: 10.1093/braincomms/fcab039. eCollection 2021.

  PMID: 33928247 BACKGROUND

• Trapp NT, Purgianto A, Taylor JJ, Singh MK, Oberman LM, Mickey BJ, Youssef NA, Solzbacher D, Zebley B, Cabrera LY, Conroy S, Cristancho M, Richards JR, Flood MJ, Barbour T, Blumberger DM, Taylor SF, Feifel D, Reti IM, McClintock SM, Lisanby SH, Husain MM; National Network of Depression Centers Neuromodulation Task Group. Consensus review and considerations on TMS to treat depression: A comprehensive update endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology. Clin Neurophysiol. 2025 Feb;170:206-233. doi: 10.1016/j.clinph.2024.12.015. Epub 2024 Dec 19.

  PMID: 39756350 BACKGROUND

• Subramanian S, Lopez R, Zorumski CF, Cristancho P. Electroconvulsive therapy in treatment resistant depression. J Neurol Sci. 2022 Mar 15;434:120095. doi: 10.1016/j.jns.2021.120095. Epub 2021 Dec 18.

  PMID: 34979372 BACKGROUND

• Pike AC, Robinson OJ. Reinforcement Learning in Patients With Mood and Anxiety Disorders vs Control Individuals: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2022 Apr 1;79(4):313-322. doi: 10.1001/jamapsychiatry.2022.0051.

  PMID: 35234834 BACKGROUND

• Landry M, Moreno A, Patry S, Potvin S, Lemasson M. Current Practices of Electroconvulsive Therapy in Mental Disorders: A Systematic Review and Meta-Analysis of Short and Long-Term Cognitive Effects. J ECT. 2021 Jun 1;37(2):119-127. doi: 10.1097/YCT.0000000000000723.

  PMID: 33009218 BACKGROUND

• Kuhnel A, Teckentrup V, Neuser MP, Huys QJM, Burrasch C, Walter M, Kroemer NB. Stimulation of the vagus nerve reduces learning in a go/no-go reinforcement learning task. Eur Neuropsychopharmacol. 2020 Jun;35:17-29. doi: 10.1016/j.euroneuro.2020.03.023. Epub 2020 May 11.

  PMID: 32404279 BACKGROUND

• Kamel LY, Xiong W, Gott BM, Kumar A, Conway CR. Vagus nerve stimulation: An update on a novel treatment for treatment-resistant depression. J Neurol Sci. 2022 Mar 15;434:120171. doi: 10.1016/j.jns.2022.120171. Epub 2022 Jan 29.

  PMID: 35158102 BACKGROUND

• Hewitt SRC, Norbury A, Huys QJM, Hauser TU. Day-to-day fluctuations in motivation drive effort-based decision-making. Proc Natl Acad Sci U S A. 2025 Mar 25;122(12):e2417964122. doi: 10.1073/pnas.2417964122. Epub 2025 Mar 17.

  PMID: 40096607 BACKGROUND

• Ferstl M, Kuhnel A, Klaus J, Lin WM, Kroemer NB. Non-invasive vagus nerve stimulation conditions increased invigoration and wanting in depression. Compr Psychiatry. 2024 Jul;132:152488. doi: 10.1016/j.comppsych.2024.152488. Epub 2024 Apr 16.

  PMID: 38657358 BACKGROUND

• Espinoza RT, Kellner CH. Electroconvulsive Therapy. N Engl J Med. 2022 Feb 17;386(7):667-672. doi: 10.1056/NEJMra2034954. No abstract available.

  PMID: 35172057 BACKGROUND

• Conroy SK, Holtzheimer PE. Neuromodulation Strategies for the Treatment of Depression. Am J Psychiatry. 2021 Dec;178(12):1082-1088. doi: 10.1176/appi.ajp.2021.21101034.

  PMID: 34855452 BACKGROUND

• Biernacki K, Myers CE, Cole S, Cavanagh JF, Baker TE. Prefrontal transcranial magnetic stimulation boosts response vigour during reinforcement learning in healthy adults. Eur J Neurosci. 2023 Feb;57(4):680-691. doi: 10.1111/ejn.15905. Epub 2022 Dec 30.

  PMID: 36550631 BACKGROUND

• Amlung M, Marsden E, Holshausen K, Morris V, Patel H, Vedelago L, Naish KR, Reed DD, McCabe RE. Delay Discounting as a Transdiagnostic Process in Psychiatric Disorders: A Meta-analysis. JAMA Psychiatry. 2019 Nov 1;76(11):1176-1186. doi: 10.1001/jamapsychiatry.2019.2102.

  PMID: 31461131 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Nils B Kroemer, Prof. Dr.

  Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nils B Kroemer, Prof. Dr.

CONTACT

+49 228 287 11151; nkroemer@uni-bonn.de

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. rer. nat.

Study Record Dates

• First Submitted: September 10, 2026
• First Posted: September 16, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 16, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Anonymized data will be shared upon publication of the results
• Access Criteria: Until the data is publicly available, researchers may contact the lead PI to gain access.

Locations

DE (1)