Cognitive Control Functions of the Human Thalamus

NCT06920992 | Completed Results

• 2 other identifiers: 201808855R01MH122613
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research project is to investigate how brain lesions affect our ability to generate goal-directed behaviors - a cognitive function commonly referred to as cognitive control. To support goal-directed behaviors, the human brain must adaptively direct thoughts and actions depending on the current goals and contexts. Our principal hypothesis is that this cognitive capacity depends on a brain network architecture that can flexibly transmit, select, and inhibit information along neural pathways. Therefore, lesions and damages to critical brain network components will negatively affect behavior. To faithfully assess the structure and function of human brain networks and its disruption from brain lesions, investigators will recruit healthy adult human subjects and patients with brain lesions to participate in a multi-session study that includes cognitive behavioral tests, structural magnetic resonance imaging (MRI) using a 3 Tesla (3T) scanner, and electroencephalography (EEG) studies. During all testing sessions, subjects will perform cognitive tasks that assess their ability to select, maintain, and inhibit sensory information and generate motor responses. Their eye movements may be passively recorded during testings. 3T MRI allows for fast and high-resolution imaging of brain structures, enabling us to identify lesion loci. Investigators will use EEG to measure the electrophysiology of brain activities. All behavioral, EEG, and MRI data collected will be sent to the National Institute of Mental Health Data Archive (NDA) at the National Institute of Mental Health (NIMH).

Conditions

Stroke

Keywords

Cognitive Control; Stroke; Thalamus

Outcome Measures

Primary Outcomes (2)

• Cognitive Flexibility Performance as Measured by Accuracy, in the Unit of Percentage of Correct Responses

  The accuracy measure of the behavioral task will determine whether the hypothesized cognitive function of cognitive flexibility is implemented by a hierarchical cognitive control model instantiated in the human thalamus. A lower accuracy scale for the extradimensional shift condition (EDS) relative to other conditions would suggest increased difficulty in engaging in cognitive flexibility. The scale is from 0 to 100.

  2 weeks

• Measure of Thalamus Response to Cognitive Flexibility, in the Unit of fMRI BOLD Signal Increase Relative to no Stimulus Presentation.

  When subjects perform the cognitive flexibility task, we can then measure how strongly the medial thalamus responds to different task conditions. The signal scale will be in beta coefficients measured by fMRI BOLD response. This is a measurement of relative signal increase in response to the presented task. A higher beta value for the thalamus for the extradimensional shift condition would indicate thalamus involvement in cognitive flexibility. The scale is from -100 to 100

  2 hours

Secondary Outcomes (1)

• EEG Oscillations in the Theta Frequency Band, in the Unit of Signal Increase Relative to Recordings From no Stimulus Presentation.

  2hrs

Study Arms (1)

Determine how the thalamus contributes to cognitive control

EXPERIMENTAL

We conducted cognitive behavioral testing on cognitive flexibility using EEG, fMRI and behavioral experiments. The intervention for all three methods (EEG, fMRI, behavioral) were the same, subjects performed a cognitive flexibility task with three conditions: extradimensional shift, intradimensional shift, and no switching condition. With all three experiments we can measure the behavioral accuracy. With fMRI we can measure evoked fMRI response amplitude in the thalamus, with EEG we can measure scalp voltage signal in patients.

Behavioral: measuring cognitive flexibility including working memory and set-switching

Interventions

measuring cognitive flexibility including working memory and set-switching BEHAVIORAL

A behavioral task that requires subjects to switch between stimulus- response contingencies based on a colored contextual cue. In addition, this task requires subjects to memorize a set of visual stimuli. Subjects will then be presented with a test set and will be asked to indicate whether any stimulus therein is not part of original memorized set. Three conditions will be measured, including EDS (extradimensional shift), IDS (intradimensionaly shift), and Stay (no switching).

Determine how the thalamus contributes to cognitive control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults age 18-35 without neurological or psychological disorders. No metal implants. No Claustrophobia.
• Patients with focal lesions within the thalamus. Age 18 or older. No diagnosis of psychiatric disorders. No metal implants. No Claustrophobia.
• Patients with focal lesions that spare the frontal and parietal cortices. Age 18 or older. No diagnosis of psychiatric disorders.
• No metal implants. No Claustrophobia.

You may not qualify if:

• claustrophobic Psychiatric conditions such as depression and ADHD. Implanted device such as cardia pacemakers and autodefbrillaotors, aneurysm, cochlear implants.
• Not fluent in English.

Sponsors & Collaborators

• Kai Hwang: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

The University of Iowa

Iowa City, Iowa, 52246, United States

Location

Related Publications (5)

• 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

• Cellier D, Petersen IT, Hwang K. Dynamics of Hierarchical Task Representations. J Neurosci. 2022 Sep 21;42(38):7276-7284. doi: 10.1523/JNEUROSCI.0233-22.2022.

  PMID: 35985836 RESULT

• 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 RESULT

• Hwang K, Shine JM, Bruss J, Tranel D, Boes A. Neuropsychological evidence of multi-domain network hubs in the human thalamus. Elife. 2021 Oct 8;10:e69480. doi: 10.7554/eLife.69480.

  PMID: 34622776 RESULT

• 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 RESULT

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Kai Hwang, PhD
• Organization: University of Iowa

kai-hwang@uiowa.edu

3194670609

Publication Agreements

• PI is Sponsor Employee: Yes

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: Compare patients with stroke with healthy comparisons

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: April 10, 2025
• Study Start: March 10, 2020
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: September 15, 2026
• Results First Posted: September 15, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)