Investigating the Mechanisms of Decision-Making Using Non-Invasive Brain Stimulation
StimMaps_YH
Investigating the Interplay of Striatal and Hippocampal Processing in Decision-Making Using Transcranial Temporal Interference Stimulation
1 other identifier
interventional
36
1 country
1
Brief Summary
This study aims to investigate which of two brain regions is important for which decision-making strategy. The investigators suppose that one brain region - the \*striatum\* - is important for repeatedly choosing objects that have previously been paired with rewards (strategy 1). They suppose that a different region - the \*hippocampus\* - is important for extending such reasoning to RELATED objects (strategy 2). The investigators will repeatedly ask young and healthy subjects to choose between two objects. The two objects are repeatedly drawn from a pool of seven. Relations between the seven objects have been learned on the first day of the experiment. The investigators will record subjects' choices and will use an automated way to assess the extent to which any given subject uses either decision-making strategy.
- On one day, subjects will perform the task while their right hippocampus is being stimulated with non-invasive electrical stimulation ("condition A").
- On another day, subjects will perform the same task but with their striatum being stimulated ("condition B").
- On yet another day, a control stimulation ("condition C") will be applied that looks and feels like the real stimulation but does not influence brain activity. Which stimulation (A, B, C) happens on which day is assigned by computer code and differs between subjects. Subjects do not know, and investigators mostly do not know, whether real or control stimulation is applied on each day. The investigators will check whether subjects use strategy 1 more when their striatum is being stimulated and strategy 2 more when their hippocampus is being stimulated, as compared to when the control stimulation is applied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Apr 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 27, 2026
CompletedFirst Submitted
Initial submission to the registry
June 26, 2026
CompletedFirst Posted
Study publicly available on registry
August 6, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 1, 2027
August 6, 2026
August 1, 2026
11 months
June 26, 2026
August 2, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Weight between map-based generalization and stimulus-outcome association-based decision-making
"Weight" references a parameter that is extracted from recorded choice behavior by means of computational modeling. Three basic models (one map-based, two stimulus-outcome association-based) are fit to each subject's choice data from each session. Two hybrid models - combining the map-based with either of the stimulus-outcome association-based components - are also fit. The weight parameter will be extracted from the hybrid model that fits most subjects' behavior best under the control condition (high-frequency stimulation). It describes the extent to which the subject relies on the map-based relative to the association-based component/strategy for making their choices. Given the presumed roles of hippocampus in map-based and striatum in association-based decision-making, the investigators expect the weight parameter to increase under hippocampal tTIS and to decrease under striatal tTIS relative to high-frequency control stimulation.
Days 2-4.
Secondary Outcomes (9)
Choice accuracy
Days 2-4.
Choice response time
Days 2-4.
Proportion of subjects best fit by different computational models
Days 2-4.
Influence of true and past rewards on choice
Days 2-4.
Influence of true and past rewards on choice response time
Days 2-4.
- +4 more secondary outcomes
Other Outcomes (7)
Gender
Day 1.
Age
Day 1.
Center for Epidemiological Studies Depression Scale
Day 1.
- +4 more other outcomes
Study Arms (12)
Striatal tTIS -> Hippocampal tTIS -> Striatal high-frequency control
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Striatal" in "striatal high-frequency control" refers to the electrode set-up (no actual stimulation of the striatum occurs in that condition).
Striatal tTIS -> Striatal high-frequency control -> Hippocampal tTIS
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Striatal" in "striatal high-frequency control" refers to the electrode set-up (no actual stimulation of the striatum occurs in that condition).
Hippocampal tTIS -> Striatal high-frequency control -> Striatal tTIS
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Striatal" in "striatal high-frequency control" refers to the electrode set-up (no actual stimulation of the striatum occurs in that condition).
Hippocampal tTIS -> Striatal tTIS -> Striatal high-frequency control
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Striatal" in "striatal high-frequency control" refers to the electrode set-up (no actual stimulation of the striatum occurs in that condition).
Striatal high-frequency control -> Striatal tTIS -> Hippocampal tTIS
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Striatal" in "striatal high-frequency control" refers to the electrode set-up (no actual stimulation of the striatum occurs in that condition).
Striatal high-frequency control -> Hippocampal tTIS -> Striatal tTIS
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Striatal" in "striatal high-frequency control" refers to the electrode set-up (no actual stimulation of the striatum occurs in that condition).
Striatal tTIS -> Hippocampal tTIS -> Hippocampal high-frequency control
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Hippocampal" in "hippocampal high-frequency control" refers to the electrode set-up (no actual stimulation of the hippocampus occurs in that condition).
Striatal tTIS -> Hippocampal high-frequency control -> Hippocampal tTIS
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Hippocampal" in "hippocampal high-frequency control" refers to the electrode set-up (no actual stimulation of the hippocampus occurs in that condition).
Hippocampal tTIS -> Hippocampal high-frequency control -> Striatal tTIS
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Hippocampal" in "hippocampal high-frequency control" refers to the electrode set-up (no actual stimulation of the hippocampus occurs in that condition).
Hippocampal tTIS -> Striatal tTIS -> Hippocampal high-frequency control
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Hippocampal" in "hippocampal high-frequency control" refers to the electrode set-up (no actual stimulation of the hippocampus occurs in that condition).
Hippocampal high-frequency control -> Striatal tTIS -> Hippocampal tTIS
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Hippocampal" in "hippocampal high-frequency control" refers to the electrode set-up (no actual stimulation of the hippocampus occurs in that condition).
Hippocampal high-frequency control -> Hippocampal tTIS -> Striatal tTIS
EXPERIMENTALStriatal tTIS and hippocampal tTIS are active experimental conditions. High-frequency control is a placebo comparator. "Hippocampal" in "hippocampal high-frequency control" refers to the electrode set-up (no actual stimulation of the hippocampus occurs in that condition).
Interventions
Transcranial temporal interference stimulation using intermittent theta-burst protocol and targeting right hippocampus. Unlike the striatal set-up, the hippocampal electrode set-up is asymmetrical and can only stimulate unilaterally (Beanato, Moon et al., 2024; Violante et al., 2023). In the present study, \*right\* hippocampus is targeted because it showed cognitive map-compatible activity in a similar task in a previous study (Garvert et al., 2023) and because it has been suggested to be involved in map-based navigation (IglĂ³i et al., 2010).
Transcranial temporal interference stimulation using intermittent theta-burst protocol and targeting bilateral striatum.
Analoguous to transcranial temporal interference stimulation except both high-frequency electric fields are oscillating at the exact same frequency, meaning there is no biologically active envelope modulation. This high-frequency stimulation is applied with the striatal electrode set-up in 50 % of the subjects (hippocampal set-up in the other 50 %). No stimulation actually occurs because the stimulation frequency is too high to be biologically active (Grossman et al., 2017).
Analoguous to transcranial temporal interference stimulation except both high-frequency electric fields are oscillating at the exact same frequency, meaning there is no biologically active envelope modulation. This high-frequency stimulation is applied with the hippocampal electrode set-up in 50 % of the subjects (striatal set-up in the other 50 %). No stimulation actually occurs because the stimulation frequency is too high to be biologically active (Grossman et al., 2017).
Eligibility Criteria
You may qualify if:
- No diagnosis of any neurological or psychiatric disease
You may not qualify if:
- Severe neuropsychiatric or unstable systemic disease
- Severe sensory or cognitive impairment or musculoskeletal dysfunction that would prevent subjects from understanding the task instructions or executing the tasks
- Implanted medical devices
- Diagnosis of epilepsy or history of one or more epileptic seizure(s)
- Pieces of metal in/around the head
- Regular consumption of narcotics (also excluded: cannabis within past month, alcohol abuse or dependence)
- Pregnancy and breast feeding
- Incapability of giving informed consent
- Left-handedness
- Subjects included in the study will be excluded from analyses if their datasets are incomplete. To ensure full counterbalancing, excluded subjects will be replaced by new ones.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Wuerzburg University Hospitallead
- University of Wuerzburgcollaborator
Study Sites (1)
University Hospital WĂ¼rzburg (UKW)
WĂ¼rzburg, Bavaria, 97080, Germany
Related Publications (13)
Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971 Mar;9(1):97-113. doi: 10.1016/0028-3932(71)90067-4. No abstract available.
PMID: 5146491BACKGROUNDGarvert MM, Saanum T, Schulz E, Schuck NW, Doeller CF. Hippocampal spatio-predictive cognitive maps adaptively guide reward generalization. Nat Neurosci. 2023 Apr;26(4):615-626. doi: 10.1038/s41593-023-01283-x. Epub 2023 Apr 3.
PMID: 37012381BACKGROUNDIgloi K, Doeller CF, Berthoz A, Rondi-Reig L, Burgess N. Lateralized human hippocampal activity predicts navigation based on sequence or place memory. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14466-71. doi: 10.1073/pnas.1004243107. Epub 2010 Jul 26.
PMID: 20660746BACKGROUNDHautzinger, M., & Bailer, M. (2003). Allgemeine Depressions-Skala (ADS) [Test]. Beltz-Test.
BACKGROUNDBeanato E, Moon HJ, Windel F, Vassiliadis P, Wessel MJ, Popa T, Pauline M, Neufeld E, De Falco E, Gauthier B, Steiner M, Blanke O, Hummel FC. Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans. Sci Adv. 2024 Nov;10(44):eado4103. doi: 10.1126/sciadv.ado4103. Epub 2024 Oct 30.
PMID: 39475597BACKGROUNDVassiliadis P, Beanato E, Popa T, Windel F, Morishita T, Neufeld E, Duque J, Derosiere G, Wessel MJ, Hummel FC. Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills. Nat Hum Behav. 2024 Aug;8(8):1581-1598. doi: 10.1038/s41562-024-01901-z. Epub 2024 May 29.
PMID: 38811696BACKGROUNDVassiliadis P, Stiennon E, Windel F, Wessel MJ, Beanato E, Hummel FC. Safety, tolerability and blinding efficiency of non-invasive deep transcranial temporal interference stimulation: first experience from more than 250 sessions. J Neural Eng. 2024 Mar 11;21(2). doi: 10.1088/1741-2552/ad2d32.
PMID: 38408385BACKGROUNDWatanabe, S. (2010). Asymptotic Equivalence of Bayes Cross Validation and Widely Applicable Information Criterion in Singular Learning Theory. Journal of Machine Learning Research, 11, 3571-3594.
BACKGROUNDWessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park CH, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FC. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat Neurosci. 2023 Nov;26(11):2005-2016. doi: 10.1038/s41593-023-01457-7. Epub 2023 Oct 19.
PMID: 37857774BACKGROUNDViolante IR, Alania K, Cassara AM, Neufeld E, Acerbo E, Carron R, Williamson A, Kurtin DL, Rhodes E, Hampshire A, Kuster N, Boyden ES, Pascual-Leone A, Grossman N. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat Neurosci. 2023 Nov;26(11):1994-2004. doi: 10.1038/s41593-023-01456-8. Epub 2023 Oct 19.
PMID: 37857775BACKGROUNDGrossman N, Bono D, Dedic N, Kodandaramaiah SB, Rudenko A, Suk HJ, Cassara AM, Neufeld E, Kuster N, Tsai LH, Pascual-Leone A, Boyden ES. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields. Cell. 2017 Jun 1;169(6):1029-1041.e16. doi: 10.1016/j.cell.2017.05.024.
PMID: 28575667BACKGROUNDGlascher J, Daw N, Dayan P, O'Doherty JP. States versus rewards: dissociable neural prediction error signals underlying model-based and model-free reinforcement learning. Neuron. 2010 May 27;66(4):585-95. doi: 10.1016/j.neuron.2010.04.016.
PMID: 20510862BACKGROUNDGarvert MM, Dolan RJ, Behrens TE. A map of abstract relational knowledge in the human hippocampal-entorhinal cortex. Elife. 2017 Apr 27;6:e17086. doi: 10.7554/eLife.17086.
PMID: 28448253BACKGROUND
Study Officials
- PRINCIPAL INVESTIGATOR
Maximilian J. Wessel, Prof. Dr.
University Hospital WĂ¼rzburg (UKW)
- PRINCIPAL INVESTIGATOR
Mona M. Garvert, Prof. Dr.
Julius-Maximilians-Universität WĂ¼rzburg (JMU)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- All parties are blind to the type of stimulation (tTIS vs. high-frequency control stimulation). The investigator arranges and the subject experiences - they are hence not blind to - the electrode set-up (hippocampal vs. striatal). In the event that a given subject has already received the hippocampal set-up in their first two sessions, the investigator may conclude that the unique striatal set-up in this particular subject's third session must be associated with real (= temporal interference) rather than control stimulation. This is because each brain region must receive the real stimulation exactly once. This limitation to blinding applies whenever the unique set-up (= the one that a given subject receives only once instead of twice) is administered in the LAST of the three sessions (because it is only then that the investigator may know which one is the unique set-up). This will be true in one-third of the subjects and will equally concern hippocampal and striatal stimulations.
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr.
Study Record Dates
First Submitted
June 26, 2026
First Posted
August 6, 2026
Study Start
April 27, 2026
Primary Completion (Estimated)
April 1, 2027
Study Completion (Estimated)
April 1, 2027
Last Updated
August 6, 2026
Record last verified: 2026-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ANALYTIC CODE
- Time Frame
- Data and supporting information will be made available upon publication of the manuscript without end date.
- Access Criteria
- Anonymized data as specified above will be made freely accessible in an online repository. Further supporting information will be shared with researchers upon request to the corresponding author.
Each subject's age, gender, depression score, handedness score, learning performance, and choice data under each stimulation condition will be shared (from which response times, choice accuracy, and decision-making strategies may be extracted, the latter by means of computational modeling). Non-freetext stimulation sensation ratings, side effect reports, and blinding check data will also be shared. Data will be shared in anonymized form.