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

Официальное название

Investigating the Interplay of Striatal and Hippocampal Processing in Decision-Making Using Transcranial Temporal Interference Stimulation

Обзор

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.

Подробное описание

The purpose of this study is to isolate the roles of hippocampal formation versus striatum in cognitive map-based versus stimulus-outcome learning-based decision-making. The study consists of four sessions on four consecutive days: an initial learning session and three decision-making sessions under three different non-invasive brain stimulation conditions.

Decision-making will be observed in a choice task, where young and healthy adults will be presented with two out of seven stimuli on any given trial. They will be asked to choose one of both so as to maximize their reward. The reward value of the chosen stimulus is displayed after the choice has been made. Different stimuli's reward values are related to each other following latent relations between stimuli learned during the subject's first experimental session. Throughout the choice task, reward values shift from time to time without notice, but always respecting the latent structure between stimuli. Subjects can most successfully adapt to these spontaneous shifts if they use the relational knowledge acquired during session 1 (map-based generalization), whereas learning the new reward values one-by-one will cost more time/trials (stimulus-outcome association learning).

During the choice task, neural activity will be upregulated using transcranial temporal interference stimulation (tTIS; Grossman et al., 2017; Vassiliadis et al., 08/2024), specifically, intermittent theta-burst stimulation (iTBS; Beanato, Moon et al., 2024; Wessel, Beanato et al., 2023). Subjects will undergo hippocampal tTIS in one session, striatal tTIS in another session, and high-frequency control stimulation in yet another session. The order of conditions is pseudorandomized and counterbalanced across subjects. For blinding, see "Study Design". Shifts in cognitive map-based versus stimulus-outcome association-based decision-making will be analyzed as a function of stimulation condition using computational modeling of choice data.

Assuming a causal role of the hippocampal formation in cognitive map-based behavior (Garvert et al., 2017) and of the striatum in stimulus-outcome learning (Gläscher et al., 2010), a double dissociation may be expected: upregulating hippocampal activity should boost map-based over stimulus-outcome association-based decision-making, whereas upregulating striatal activity should produce the opposite effect (always as compared to the high-frequency control stimulation).

Hypotheses formulated in this registration are theoretically motivated and partly supported by online behavioral pilot data that will not be included in any analyses. At first submission of this registration, data collection is ongoing. The collected data has been inspected for quality control but has neither been used to generate hypotheses nor to test these (except navigation and proximity judgment task accuracy has been inspected to ensure successful learning). Investigators are partly blind to stimulation condition (see "Study Design"), and no stimulation condition-dependent analyses have been conducted before submission of this registration.

Вмешательства

• Устройство 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 invol
• Устройство Striatal intermittent-theta burst stimulation
  Transcranial temporal interference stimulation using intermittent theta-burst protocol and targeting bilateral striatum.
• Устройство 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).
• Устройство 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).

Первичные конечные точки

• Weight between map-based generalization and stimulus-outcome association-based decision-making [Срок оценки: Days 2-4.]

Вторичные конечные точки (9)

• Choice accuracy [Срок оценки: Days 2-4.]
• Choice response time [Срок оценки: Days 2-4.]
• Proportion of subjects best fit by different computational models [Срок оценки: Days 2-4.]
• Influence of true and past rewards on choice [Срок оценки: Days 2-4.]
• Influence of true and past rewards on choice response time [Срок оценки: Days 2-4.]
• Proximity judgment task accuracy [Срок оценки: Days 1-4.]
• Proximity judgment task response time [Срок оценки: Days 1-4.]
• Stimulation tolerability [Срок оценки: Days 2-4.]
• Stimulation blinding [Срок оценки: Day 4.]

Критерии участия

Критерии включения

• No diagnosis of any neurological or psychiatric disease

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Германия · 1 центр

• University Hospital Würzburg (UKW) — Würzburg

Публикации

• 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 5146491
• Garvert 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 37012381
• Igloi 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 20660746
• Hautzinger, M., & Bailer, M. (2003). Allgemeine Depressions-Skala (ADS) [Test]. Beltz-Test.
• Beanato 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 39475597
• Vassiliadis 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 38811696
• Vassiliadis 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 38408385
• Watanabe, 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.

Идентификаторы

NCT: NCT07749378 · 2025-313-dvha

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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