Investigating the Mechanisms of Decision-Making Using Non-Invasive Brain Stimulation

Condition(s) studied

Investigational drug(s) / intervention(s)

Hippocampal intermittent-theta burst stimulation: 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 (Iglói et al., 2010).

Striatal intermittent-theta burst stimulation: Transcranial temporal interference stimulation using intermittent theta-burst protocol and targeting bilateral striatum.

High-frequency control stimulation with striatal electrode set-up: 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).

High-frequency control stimulation with hippocampal electrode set-up: 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).

Study 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.

Eligibility

Primary outcome measure(s)

• Weight between map-based generalization and stimulus-outcome association-based decision-making — Days 2-4.
  "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.

Trial sites (1)

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