HealthyNCT07199907
Hippocampal and Frontoparietal Development and Inference
A study testing Associative Inference and Probabilistic Inference in people with Healthy, run by University of Texas at Austin at 1 site in United States.
Trial summary
The goal of this clinical trial is to test if an intervention used to manipulate memory and inference can improve our understanding of how brain development supports these abilities in healthy adolescent and adult volunteers. Read more about this study
- Who is it for?
- Ages 13 to 25 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Associative Inference and Probabilistic Inference
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Feb 2025to Aug 2029
- 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 13 to 25 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Right-handed
- Have normal or corrected to normal vision
- Have normal hearing
- Do not have contraindications for MRI
- Have no history of neurological or psychiatric disorders at initial intake
- Are of normal intelligence
- Native or fluent English speaker
Who cannot join
- A major medical illness or a neurological disorder, or neurological abnormality including significant head trauma (loss of consciousness > 5 min).
- Meeting criteria for any psychiatric disorder or any prior psychiatric hospitalizations
- Intelligence scores more than 1 standard deviation below the mean on the WASI-II
- History of special education placement
- Non-native English speaker
- Prior use of psychotropic medication, except antidepressants, for longer than 1 month
- History of moderate to severe cannabis use disorder, via self-report
- MRI exclusions: Claustrophobia; tattoos above the shoulders; permanent eyeliner; permanent retainer or spacer; artificial eyebrows; cardiac pacemaker; metal fragments in eye, skin, or body, including shrapnel; heart valve replacement; brain clips; venous umbrella; being a sheet-metal worker or welder; lifetime history of aneurysm surgery; intracranial bypass, renal, or aortic clips; prosthetic devices such as middle ear, eye, joint, or penile implants; joint replacements; non-removable hearing aid, neurostimulator, or insulin pump; shunts/stents; metal mesh/coil implants; metal plate/pin/screws/wires; or any other metal implants; or suspected pregnancy.
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 Texas at Austin
Austin, Texas, 78712
Alison R Preston, PhD, 512-475-7255, apreston@utexas.edu
Nicole L Varga, PhD, 856-304-6771, nvarga@austin.utexas.edu
About this study
Official title: Hippocampal and Frontoparietal Mechanisms of Knowledge Acquisition and Inference
The goal of this clinical trial is to test if an intervention used to manipulate memory and inference can improve our understanding of how brain development supports these abilities in healthy adolescent and adult volunteers. The main questions it aims to answer are: (1) Do hippocampus and ventromedial prefrontal cortex shift from forming simple memories for singular experiences to more complex memories that link numerous experiences together?; (2) Does an improved ability to retrieve prior memories in parietal cortex during new learning have consequences for how those memories are organized at different ages?; and (3) Does the emerging memory control supported by ventromedial prefrontal cortex development facilitate the formation of optimally-organized memory representations? Adolescent participants (13-18 years) will perform two experimental tasks during functional magnetic resonance imaging (fMRI) scanning at three timepoints (T1-T3), spaced 1.5 years apart. Researchers will compare behavioral and neuroimaging data to a separate group of adults (19-25 years) who will perform the task at a single timepoint (T1). The tasks and comparison groups will allow us to isolate the neural processes that support memory and inference behavior, and how these processes change with age.
Read the detailed description
Hippocampus (HPC) structure and its connectivity with frontoparietal regions continue to develop through adolescence, a developmental period associated with substantial gains in memory and reasoning. While such structural changes are well documented, we know less about the functions that HPC and frontoparietal development confer, fundamentally limiting our understanding of the mechanisms through which individuals learn and reason about the world at different ages. From very early in life, children can learn simple associations that they directly experience. However, with age, our memories become more complex, reflecting not only directly observed information, but also knowledge derived across multiple episodes. Such derived knowledge might represent commonalities among experiences while simultaneously exaggerating important differences between them, thus forming hierarchical knowledge structures that can support inference decisions about event relationships, while also preserving detailed memory for when and where those relationships vary by context. The overarching goal of this proposal is to test the hypothesis that representational capacity within HPC and frontoparietal cortex undergoes qualitative changes during adolescence. We will use a serial cohort design to collect data from adolescents (13-18 years) at three timepoints, each 1.5 years apart, as well as data from adults (19-25 years) at a single timepoint. This design will allow us to test longitudinal predictions about how changes in neural representation within individual adolescents, over time, predict corresponding changes in memory and inference behaviors, as well as cross-sectional predictions about how HPC and frontoparietal cortex representation differs between adolescents and adults. We will use high-resolution functional magnetic resonance imaging (fMRI), representational fMRI analyses, and computational modeling, to test three Aims. Aim 1 will test the prediction that HPC and ventromedial prefrontal (vmPFC) representations will transition from coding simple, individual associations to extracting hierarchical knowledge about the relationships among experiences. Aim 2 will test the prediction that lateral parietal cortex (LPC)-mediated memory reactivation during new learning and inference will have different consequences for HPC-vmPFC representation and inference behavior at distinct points in adolescence. Aim 3 will test the prediction that emerging vmPFC control will influence what memories are available in LPC during learning and inference, as well as directly mediate the impact reactivated memories have on the trajectory of HPC representation during adolescence. The results from this project will provide a key test of fundamental theories of cognitive development and substantially advance our knowledge of the representational capacities of the HPC-frontoparietal memory system in typically developing adolescents. In doing so, the findings may have important implications for our eventual understanding of how the onset of mental health disorders (e.g., affective disorders and schizophrenia) during adolescence impact neural representation as well as memory and reasoning ability.
- Conditions
- Healthy
- Being tested
- Associative Inference, Probabilistic Inference
- Keywords
- Hippocampus, Medial Prefrontal Cortex, Parietal Cortex, Memory, Reasoning, Inference, Adolescence, Brain Development
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Associative InferenceBehavioural
Objects, faces, and scenes will be arranged into 12 ABC triads presented as overlapping AB and BC pairs. AB pairs will comprise objects; BC pairs will consist of the same B object paired with a face or scene (C). Twelve non-overlapping (NO) pairs will serve as controls. Participants will study overlapping (AB, BC) and NO pairs (4s) across two 5-minute fMRI runs. Each pair will be presented three times within a run. Following learning, participants will complete a self-paced 3-alternative forced choice (AFC) inference task during which they will select the C item that shares a common relationship with an A cue. Foils for inference trials will be C items from other ABC triads, of the same face/scene subcategory. Participants will then complete a final, self-paced 3-AFC memory test of premise associations (AB, BC) and NO pairs. To quantify memory retrieval and how overlapping events are organized, before and after learning, participants will view the A and C items during fMRI scanning.
Probabilistic InferenceBehavioural
Participants will visit a virtual "zoo," which is divided into three zones, each containing the same five monsters, but with different likelihoods of occurrence. Participants learn the underlying likelihood distributions by virtually navigating each zone. On each trial, two monsters appear; participants select the monster that they predict will next appear (6s). After making their choice, the correct monster appears and feedback is provided (2s). Participants tour each zone four times across 9 runs. Following learning, participants are tested on probabilistic inference. Here, participants see a series of monster "photographs" and are asked to infer in which zone they were taken. On each trial, a sequence of individual monster images (3.5s each) will then appear (1-6 monsters) prior to a decision screen, in which participants choose which of the two zones most likely produced the "photos" (4s) and are given feedback (1.5s). Participants will perform nine fMRI runs of the inference task.
| Study group | Role | What they receive |
|---|---|---|
| Adolescents | Experimental | Participants completed a predictable (associative inference; Session 1) and noisy (probabilistic inference; Session 2) learning task during fMRI scanning. Participants completed these tasks three times, once every 18 months. Receives: Behavioral: Associative Inference; Behavioral: Probabilistic Inference |
| Adults | Experimental | Participants completed a predictable (associative inference; Session 1) and noisy (probabilistic inference; Session 2) learning task during fMRI scanning. Participants completed these tasks a single time, serving as a control comparison to our adolescent arm. Receives: Behavioral: Associative Inference; Behavioral: Probabilistic Inference |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in blood oxygen-level dependent (BOLD) signal over time
Within the adolescent group, changes in BOLD signal during task performance, as measured by functional magnetic resonance imaging (fMRI), will be assessed across three separate timepoints.
Measured: 36 months
Differences in blood oxygen-level dependent (BOLD) signal between age groups
Differences in BOLD signal during task performance, as measured by functional magnetic resonance imaging (fMRI), will be compared between the adolescent and adult groups at timepoint 1.
Measured: 1 month
Secondary outcomes (2)
Changes in task behavior over time
Within the adolescent group, changes in task performance, as measured by the two behavioral interventions, will be assessed across three separate timepoints.
Measured: 36 months
Differences in task behavior between age groups
Differences in task performance, as measured by the two behavioral interventions, will be compared between the adolescent and adult groups at timepoint 1.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2025
- Study start20 Feb 2025
- Primary completionAug 2029 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 142 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Texas at Austin
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Nicole Varga
- Responsible party
- Principal investigator, Alison Preston, University of Texas at Austin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07199907
- Sponsor's protocol ID
- 2012090055
- Other IDs
- 5R01MH100121
- Status last verified
- Sep 2025
- First submitted
- 22 Sep 2025
- Last updated
- 30 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The present research will generate magnetic resonance imaging (MRI) data and associated electronic records of task behavior, standardized assessments, and magnetic resonance images, along with statistical maps of brain regions involved in task performance. Data and analysis code will be shared on public repositories (e.g., OSF, NDA). Data will be formatted in the standard brain imaging data structure (BIDS) format, which includes comprehensive metadata and is compatible with many analysis packages, promoting reuse of data for future projects. Raw neuroimaging data will also be shared on NDA. Results and conclusions will also be shared via peer-reviewed publications and presentations at scientific meetings such as the annual meetings of the Society for Neuroscience, the Cognitive Neuroscience Society, and Flux: The Society for Developmental Cognitive Neuroscience.
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hippocampal and Frontoparietal Mechanisms of Knowledge Acquisition and Inference
- ClinicalTrials.gov ID
- NCT07199907
- Acronym / sponsor ID
- 2012090055
- Conditions
- Healthy
- Keywords
- Hippocampus, Medial Prefrontal Cortex, Parietal Cortex, Memory, Reasoning, Inference, Adolescence, Brain Development
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 142 participants (estimated)
- Lead sponsor
- University of Texas at AustinUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Nicole Varga
- Study start
- 20 Feb 2025 (actual)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 30 Sep 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 clinical trial is to test if an intervention used to manipulate memory and inference can improve our understanding of how brain development supports these abilities in healthy adolescent and adult volunteers. The main questions it aims to answer are: (1) Do hippocampus and ventromedial prefrontal cortex shift from forming simple memories for singular experiences to more complex memories that link numerous experiences together?; (2) Does an improved ability to retrieve prior memories in parietal cortex during new learning have consequences for how those memories are organized at different ages?; and (3) Does the emerging memory control supported by ventromedial prefrontal cortex development facilitate the formation of optimally-organized memory representations? Adolescent participants (13-18 years) will perform two experimental tasks during functional magnetic resonance imaging (fMRI) scanning at three timepoints (T1-T3), spaced 1.5 years apart. Researchers will compare behavioral and neuroimaging data to a separate group of adults (19-25 years) who will perform the task at a single timepoint (T1). The tasks and comparison groups will allow us to isolate the neural processes that support memory and inference behavior, and how these processes change with age.
Detailed description
Hippocampus (HPC) structure and its connectivity with frontoparietal regions continue to develop through adolescence, a developmental period associated with substantial gains in memory and reasoning. While such structural changes are well documented, we know less about the functions that HPC and frontoparietal development confer, fundamentally limiting our understanding of the mechanisms through which individuals learn and reason about the world at different ages. From very early in life, children can learn simple associations that they directly experience. However, with age, our memories become more complex, reflecting not only directly observed information, but also knowledge derived across multiple episodes. Such derived knowledge might represent commonalities among experiences while simultaneously exaggerating important differences between them, thus forming hierarchical knowledge structures that can support inference decisions about event relationships, while also preserving detailed memory for when and where those relationships vary by context. The overarching goal of this proposal is to test the hypothesis that representational capacity within HPC and frontoparietal cortex undergoes qualitative changes during adolescence. We will use a serial cohort design to collect data from adolescents (13-18 years) at three timepoints, each 1.5 years apart, as well as data from adults (19-25 years) at a single timepoint. This design will allow us to test longitudinal predictions about how changes in neural representation within individual adolescents, over time, predict corresponding changes in memory and inference behaviors, as well as cross-sectional predictions about how HPC and frontoparietal cortex representation differs between adolescents and adults. We will use high-resolution functional magnetic resonance imaging (fMRI), representational fMRI analyses, and computational modeling, to test three Aims. Aim 1 will test the prediction that HPC and ventromedial prefrontal (vmPFC) representations will transition from coding simple, individual associations to extracting hierarchical knowledge about the relationships among experiences. Aim 2 will test the prediction that lateral parietal cortex (LPC)-mediated memory reactivation during new learning and inference will have different consequences for HPC-vmPFC representation and inference behavior at distinct points in adolescence. Aim 3 will test the prediction that emerging vmPFC control will influence what memories are available in LPC during learning and inference, as well as directly mediate the impact reactivated memories have on the trajectory of HPC representation during adolescence. The results from this project will provide a key test of fundamental theories of cognitive development and substantially advance our knowledge of the representational capacities of the HPC-frontoparietal memory system in typically developing adolescents. In doing so, the findings may have important implications for our eventual understanding of how the onset of mental health disorders (e.g., affective disorders and schizophrenia) during adolescence impact neural representation as well as memory and reasoning ability.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adolescents | Experimental | Behavioral: Associative Inference, Behavioral: Probabilistic InferenceParticipants completed a predictable (associative inference; Session 1) and noisy (probabilistic inference; Session 2) learning task during fMRI scanning. Participants completed these tasks three times, once every 18 months. |
| Adults | Experimental | Behavioral: Associative Inference, Behavioral: Probabilistic InferenceParticipants completed a predictable (associative inference; Session 1) and noisy (probabilistic inference; Session 2) learning task during fMRI scanning. Participants completed these tasks a single time, serving as a control comparison to our adolescent arm. |
Who may qualify
- Ages
- 13 to 25 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Right-handed
- Have normal or corrected to normal vision
- Have normal hearing
- Do not have contraindications for MRI
- Have no history of neurological or psychiatric disorders at initial intake
Key exclusion criteria (8 listed)
- A major medical illness or a neurological disorder, or neurological abnormality including significant head trauma (loss of consciousness > 5 min).
- Meeting criteria for any psychiatric disorder or any prior psychiatric hospitalizations
- Intelligence scores more than 1 standard deviation below the mean on the WASI-II
- History of special education placement
- Non-native English speaker
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 |
|---|---|---|
| Associative InferenceObjects, faces, and scenes will be arranged into 12 ABC triads presented as overlapping AB and BC pairs. AB pairs will comprise objects; BC pairs will consist of the same B object paired with a face or scene (C). Twelve non-overlapping (NO) pairs will serve as controls. Participants will study overlapping (AB, BC) and NO pairs (4s) across two 5-minute fMRI runs. Each pair will be presented three times within a run. Following learning, participants will complete a self-paced 3-alternative forced choice (AFC) inference task during which they will select the C item that shares a common relationship with an A cue. Foils for inference trials will be C items from other ABC triads, of the same face/scene subcategory. Participants will then complete a final, self-paced 3-AFC memory test of premise associations (AB, BC) and NO pairs. To quantify memory retrieval and how overlapping events are organized, before and after learning, participants will view the A and C items during fMRI scanning. | Behavioural | Adolescents, Adults |
| Probabilistic InferenceParticipants will visit a virtual "zoo," which is divided into three zones, each containing the same five monsters, but with different likelihoods of occurrence. Participants learn the underlying likelihood distributions by virtually navigating each zone. On each trial, two monsters appear; participants select the monster that they predict will next appear (6s). After making their choice, the correct monster appears and feedback is provided (2s). Participants tour each zone four times across 9 runs. Following learning, participants are tested on probabilistic inference. Here, participants see a series of monster "photographs" and are asked to infer in which zone they were taken. On each trial, a sequence of individual monster images (3.5s each) will then appear (1-6 monsters) prior to a decision screen, in which participants choose which of the two zones most likely produced the "photos" (4s) and are given feedback (1.5s). Participants will perform nine fMRI runs of the inference task. | Behavioural | Adolescents, Adults |
Primary outcome
Changes in blood oxygen-level dependent (BOLD) signal over time
Time frame: 36 months
Within the adolescent group, changes in BOLD signal during task performance, as measured by functional magnetic resonance imaging (fMRI), will be assessed across three separate timepoints.
Differences in blood oxygen-level dependent (BOLD) signal between age groups
Time frame: 1 month
Differences in BOLD signal during task performance, as measured by functional magnetic resonance imaging (fMRI), will be compared between the adolescent and adult groups at timepoint 1.
2 secondary outcomes
Changes in task behavior over time
Time frame: 36 months
Differences in task behavior between age groups
Time frame: 1 month
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 30 Sep 2025.
- Individual participant dataSharing planned: Yes. The present research will generate magnetic resonance imaging (MRI) data and associated electronic records of task behavior, standardized assessments, and magnetic resonance images, along with statistical maps of brain regions involved in task performance. Data and analysis code will be shared on public repositories (e.g., OSF, NDA). Data will be formatted in the standard brain imaging data structure (BIDS) format, which includes comprehensive metadata and is compatible with many analysis packages, promoting reuse of data for future projects. Raw neuroimaging data will also be shared on NDA. Results and conclusions will also be shared via peer-reviewed publications and presentations at scientific meetings such as the annual meetings of the Society for Neuroscience, the Cognitive Neuroscience Society, and Flux: The Society for Developmental Cognitive Neuroscience.
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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 testing Associative Inference and Probabilistic Inference in people with Healthy, run by University of Texas at Austin 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 7 inclusion and 8 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 30 Sep 2025. 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 Alison R Preston, PhD (512-475-7255, apreston@utexas.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in blood oxygen-level dependent (BOLD) signal over time (time frame: 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Sep 2025.