SchizophreniaNCT07217652
Investigating Mediodorsal Thalamus Representations Underlying Human Cognitive Flexibility
A study of Schizophrenia and Attention Deficit Disorder With Hyperactivity (ADHD), run by Kai Hwang at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Attention Deficit Disorder With Hyperactivity (ADHD)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2025to 30 Jul 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
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- 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).
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
The University of Iowa
Iowa City, Iowa, 52242
Kai Hwang, PhD, 319-335-2406, kai-hwang@uiowa.edu
About this study
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:
Read more
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.
Read the detailed description
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.
- Being tested
- High-resolution fMRI during working memory, cognitive control, and decision-making tasks
- Keywords
- Cognitive control, working memory, decision making
- Medical subject headings
- Schizophrenia, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-resolution fMRI during working memory, cognitive control, and decision-making tasksOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: High-resolution fMRI during working memory, cognitive control, and decision-making tasks |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured throughout the MRI session (approximately 90 minutes per participant).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2025
- Study start1 Dec 2025
- Primary completion30 Jun 2030 (estimated)
- Study completion30 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kai Hwang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kai Hwang, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07217652
- Sponsor's protocol ID
- 202412272
- Status last verified
- Feb 2026
- First submitted
- 10 Oct 2025
- Last updated
- 13 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: This is a basic experimental study that involves human subjects; we do not publish our findings in ICMJE journals.
Publications
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.
PubMed 39621781Shine 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.
PubMed 37237103Hwang 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.
PubMed 32902335
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Mediodorsal Thalamus Representations Underlying Human Cognitive Flexibility
- ClinicalTrials.gov ID
- NCT07217652
- Acronym / sponsor ID
- 202412272
- Keywords
- Cognitive control, working memory, decision making
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Kai HwangUniversity, hospital or other
- Study start
- 1 Dec 2025 (actual)
- Primary completion
- 30 Jun 2030 (estimated)
- Study completion
- 30 Jul 2030 (estimated)
- First posted
- 16 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Within subject manipulation of working memory, cognitive control, and decision making | Experimental | Other: High-resolution fMRI during working memory, cognitive control, and decision-making tasksParticipants 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-resolution fMRI during working memory, cognitive control, and decision-making tasksParticipants 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. | Other | Within subject manipulation of working memory, cognitive control, and decision making |
Primary outcome
Decoding of context representations in the medial dorsal thalamus from 7 T MRI data
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- Background: PubMed 39621781Chen 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.
- Background: PubMed 37237103Shine 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.
- Background: PubMed 32902335Hwang 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.
- Individual participant dataSharing planned: No. This is a basic experimental study that involves human subjects; we do not publish our findings in ICMJE journals.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of Schizophrenia and Attention Deficit Disorder With Hyperactivity (ADHD), run by Kai Hwang at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kai Hwang, PhD (319-335-2406, kai-hwang@uiowa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decoding of context representations in the medial dorsal thalamus from 7 T MRI data (time frame: Measured throughout the MRI session (approximately 90 minutes per participant).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07217652, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.