Investigating Mediodorsal Thalamus Representations Underlying Human Cognitive Flexibility

NCT07217652 | Recruiting

• 1 other identifier: 202412272
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this basic experimental research study is to examine how the human thalamus supports flexible thinking and behavior. Specifically, the research aims to elucidate how the mediodorsal (MD) thalamus encodes and updates "context"-the mental framework that determines which rules or actions are relevant in a given situation. This work may contribute to understanding why certain psychiatric conditions, such as schizophrenia and ADHD, involve difficulties with cognitive flexibility and control. The primary research questions are: Does the MD thalamus represent the context that organizes how working memory guides task selection? Does the MD thalamus signal when context needs to be updated after a change in task demands? Do these thalamic representations support generalization to new situations or rules? Participants will complete cognitive tasks while undergoing high-resolution brain imaging using 7-Tesla MRI. The investigators will combine behavioral data, computational modeling, and advanced neuroimaging analyses to examine how the thalamus interacts with the cortex during flexible decision-making.

Conditions

Schizophrenia; Attention Deficit Disorder With Hyperactivity (ADHD)

Keywords

Cognitive control; working memory; decision making

Outcome Measures

Primary Outcomes (1)

• Decoding of context representations in the medial dorsal thalamus from 7 T MRI data

  This outcome measure will quantify the extent to which multivariate patterns of brain activity in the MD thalamus encode task context. High-resolution 7-Tesla fMRI data will be analyzed using computational modeling and multivariate pattern analysis (MVPA) techniques. The primary metric will be decoding accuracy, expressed as a percentage ranging from 0% to 100%. Decoding accuracy reflects how well task contexts for working memory, cognitive control, and decision-making can be predicted from MD thalamic activity patterns. A value of 0% indicates chance-level or poor performance, while 100% indicates perfect prediction accuracy. For each participant, decoding accuracy will be computed as a single value using the same unit of measure (percentage accuracy). This value will reflect the overall ability to decode task context from MD activity and thus serves as the primary measure of this research study.

  Measured throughout the MRI session (approximately 90 minutes per participant).

Study Arms (1)

Within subject manipulation of working memory, cognitive control, and decision making

EXPERIMENTAL

Participants will complete a series of cognitive tasks designed to engage working memory, cognitive control, and decision-making. During these tasks, participants will view stimuli and make rule-based or value-based choices that require updating and applying context to guide behavior. Brain activity will be measured using high-resolution 7-Tesla functional MRI to assess how the mediodorsal thalamus and prefrontal cortex represent and update contextual information. Computational models will link behavior and neural activity to test how thalamic signals support flexible cognition and adaptive decision-making.

Other: High-resolution fMRI during working memory, cognitive control, and decision-making tasks

Interventions

High-resolution fMRI during working memory, cognitive control, and decision-making tasks OTHER

Participants will perform a set of computerized cognitive tasks designed to test working memory, cognitive control, and decision-making while undergoing high-resolution 7-Tesla functional MRI. These tasks require participants to maintain and update contextual information, switch between rules, and make value-based choices under changing conditions. The intervention is distinguished by its integration of advanced neuroimaging with computational modeling to identify how the mediodorsal thalamus and prefrontal cortex represent, update, and generalize context. This approach allows precise mapping of thalamocortical mechanisms that support flexible cognition and goal-directed behavior.

Within subject manipulation of working memory, cognitive control, and decision making

Eligibility Criteria

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

You may qualify if:

• No history of any neurological, psychiatric, or medical condition that could affect cognition
• No use of benzodiazepines, long-acting opioids, or other psychotropic drugs that could alter cognitive performance
• Normal or corrected-to-normal vision (visual acuity)
• Normal color perception (Farnsworth-Munsell 100 Hue Test)
• Fluent in English
• No metal implants (including aneurysm clip, cardiac pacemaker, ICD, IUD, neurostimulation system, spinal cord stimulator, internal electrodes or wires, bone stimulator, ear implant, insulin or other infusion pump or device, prosthesis, artificial or prosthetic limb, shunt, vascular access port or catheter, thermodilution catheter, medication patch, radiation seeds or implants, wire mesh implant, tissue expander, surgical staples or clips or sutures, joint replacement, joint/bone pin/screw/nail/wire/plate, dentures, or non-removable hearing aid)
• No exposure to shrapnel or other-related MR contraindications
• No non-removable body piercing jewelry
• No non-removable makeup
• No history of claustrophobia
• No history of breathing problems
• Not currently pregnant or trying to get pregnant (this will be determined via self report and no records will be kept).

You may not qualify if:

• Has a history of any neurological, psychiatric, or medical condition that could affect cognition
• Use of benzodiazepines, long-acting opioids, or other psychotropic drugs that could alter cognitive performance
• Not fluent in English
• Known metal implants (including aneurysm clip, cardiac pacemaker, ICD, IUD, neurostimulation system, spinal cord stimulator, internal electrodes or wires, bone stimulator, ear implant, insulin or other infusion pump or device, prosthesis, artificial or prosthetic limb, shunt, vascular access port or catheter, thermodilution catheter, medication patch, radiation seeds or implants, wire mesh implant, tissue expander, surgical staples or clips or sutures, joint replacement, joint/bone pin/screw/nail/wire/plate, dentures, or non-removable hearing aid)
• History of claustrophobia
• Currently pregnant or trying to get pregnant (this will be determined via self report and no records will be kept).

Sponsors & Collaborators

• Kai Hwang: lead

Study Sites (1)

The University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Related Publications (3)

• Chen X, Leach SC, Hollis J, Cellier D, Hwang K. The thalamus encodes and updates context representations during hierarchical cognitive control. PLoS Biol. 2024 Dec 2;22(12):e3002937. doi: 10.1371/journal.pbio.3002937. eCollection 2024 Dec.

  PMID: 39621781 BACKGROUND

• Shine JM, Lewis LD, Garrett DD, Hwang K. The impact of the human thalamus on brain-wide information processing. Nat Rev Neurosci. 2023 Jul;24(7):416-430. doi: 10.1038/s41583-023-00701-0. Epub 2023 May 26.

  PMID: 37237103 BACKGROUND

• Hwang K, Bruss J, Tranel D, Boes AD. Network Localization of Executive Function Deficits in Patients with Focal Thalamic Lesions. J Cogn Neurosci. 2020 Dec;32(12):2303-2319. doi: 10.1162/jocn_a_01628. Epub 2020 Sep 9.

  PMID: 32902335 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders

Central Study Contacts

Kai Hwang, PhD

CONTACT

319-335-2406; kai-hwang@uiowa.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: This is a within-subject research study. Each subject's performance on working memory, cognitive control, and decision-making functions will be compared across experimental conditions within each subject.

Study Record Dates

• First Submitted: October 10, 2025
• First Posted: October 16, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): July 30, 2030
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)