Investigating Mediodorsal Thalamus Representations Underlying Human Cognitive Flexibility
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Decoding of context representations in the medial dorsal thalamus from 7 T MRI data
研究概览
简要总结
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.
详细描述
The human brain's ability to learn and execute behaviors tailored to environmental contingencies is crucial for adaptive cognition. Central to this capacity are neural representations of context, which organize the associations between sensory features and behavioral utility. Despite their significance, the neural mechanisms underlying the encoding and updating of context representations remain poorly understood. This gap in knowledge is particularly relevant for understanding cognitive deficits in psychiatric disorders such as schizophrenia and ADHD.
This research study proposes to test the hypothesis that the human mediodorsal (MD) thalamus is critical for encoding, updating, and generalizing context representations. Previous studies have shown that damage to the MD thalamus impairs task switching and working memory in humans, consistent with findings from non-human animal models. Additionally, single-unit recordings in animals reveal that MD neurons rapidly encode task context, a process dependent on the convergence of prefrontal afferents. Preliminary fMRI data indicate that the human MD thalamus tracks task context and its updates following switches. However, a critical gap exists in interpreting these results due to the lack of quantitative models and advanced neuroimaging approaches to delineate the specific representations and computations carried out by the human MD.
To address this gap, the investigators will use a computational cognitive neuroscience approach, integrating computational models with high-resolution 7T MRI and advanced neuroimaging analyses. This study has three specific aims:
Aim 1: Determine whether the MD thalamus encodes context representations that organize how working memory guides task selection.
Aim 2: Investigate whether the MD thalamus encodes context prediction errors that flexibly switch prefrontal task representations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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).
排除标准
- •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).
研究组 & 干预措施
Within subject manipulation of working memory, cognitive control, and decision making
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.
干预措施: High-resolution fMRI during working memory, cognitive control, and decision-making tasks (Other)
结局指标
主要结局
Decoding of context representations in the medial dorsal thalamus from 7 T MRI data
时间窗: Measured throughout the MRI session (approximately 90 minutes per participant).
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.
次要结局
未报告次要终点
研究者
Kai Hwang
Associate Professor
University of Iowa