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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.
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.
Aim 3: Assess whether MD context representations enable generalization to novel stimulus-response contingencies during decision-making.
For all aims, the investigators will develop computational models that specify both cognitive processes and neural implementations to predict behavior and guide neuroimaging data analyses. This study aims to establish a new conceptual and empirical framework for understanding thalamic computation in humans, with significant implications for theories of cognitive control, adaptive human behavior, and cognitive dysfunction.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kai Hwang, PhD | Contact | 319-335-2406 | kai-hwang@uiowa.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Iowa | Recruiting | Iowa City | Iowa | 52242 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39621781 | Background | 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. | |
| 37237103 | 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. |
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This is a basic experimental study that involves human subjects; we do not publish our findings in ICMJE journals.
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
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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.
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| 32902335 | 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. |