NIMH K23: Modulation of Frontoparietal Dynamics in Adolescent Working Memory Deficits

NCT ID: NCT05662280

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-01
• Study Completion Date: 2026-12-01

Brief Summary

Working memory (WM) deficits are a transdiagnostic feature of adolescent psychopathology that substantially contribute to poor clinical and functional outcomes. This proposal will utilize a multimodal neuroscientific approach to investigate whether non-invasive brain stimulation can modulate the neural mechanisms underlying adolescent WM deficits. Directly in line with NIMH priorities, the researchers will identify the contributing roles of prefrontal and parietal regions in WM processes, as well as identify optimal targets and parameters for novel brain-based treatments in adolescent psychopathology. This study is funded by the NIMH-K23

Detailed Description

Project Summary/Abstract Deficits in working memory (WM) comprise a core, transdiagnostic feature of childhood and adolescent psychopathology. WM is one of the strongest predictors of clinical and functional outcomes, yet there remains a dearth of treatments available for WM deficits. WM was historically conceptualized as solely localized to the dorsolateral prefrontal cortex, while modern technology has established the broader role of the prefrontal cortex (PFC) and posterior parietal cortex (PPC). There is evidence to suggest that PPC receives direct input from PFC, although other evidence suggests the PPC encodes incoming stimuli and feeds forward to the PFC for the initiation of control functions. I have previously found that frontoparietal theta/gamma oscillations, particularly theta-gamma coupling, is a neural mechanism underlying WM processes. Novel approaches to non-invasive brain stimulation, such as intermittent theta burst stimulation (iTBS) can now modulate these distinct oscillatory dynamics and subsequently examine possible causal or temporal relationships. This award would build on my preliminary findings and transition my career from a clinician to an independent researcher. The objective of this Patient-Oriented Research Career Development Award (K23) is to provide the necessary training for me to obtain my career goal of utilizing a multimodal neuroscientific approach to measure and modulate the neural dynamics underlying neurocognitive deficits in childhood and adolescent psychopathology. In line with NIMH priorities, the training plan proposed will build upon my clinical neuropsychology and clinical research foundation to provide comprehensive training and mentorship in two core areas: 1) Neuromodulation and 2) Computational Neuroscience. In a 2x2 factorial double-blind design, the researchers will randomize a sample of 40 adolescents (12-18 years) with WM deficits to iTBS at the left DLPFC or inferior parietal lobule (IPL). Participants will complete an active iTBS session and a sham iTBS session. The primary outcome will be theta-gamma coupling during WM demands, as measured via electroencephalography during a spatial WM task immediately before and after iTBS. Aim 1 will examine the effect of iTBS to the PPC on the encoding stage of WM, while Aim 2 will examine the effect of iTBS to the PFC on the maintenance stage of WM. Aim 3 will utilize computational neural modeling to identify the neocortical circuitry underlying oscillatory modulation. My central hypothesis is that the PFC and PPC regions have complimentary roles in executing WM processes. Further, iTBS can modulate theta-gamma coupling in these regions to improve behavioral performance. The researchers will establish a framework for modulating oscillatory dynamics in child psychiatry and set the stage for my first R01 on WM-related frontoparietal oscillatory dynamics and optimal treatment parameters for adolescent WM deficits. This will provide the foundation required to dedicate my career to measuring and modulating oscillatory abnormalities in child psychiatry.

Conditions

Working Memory

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Active intermittent Theta Burst Stimulation

In a 2x2 factorial double-blind design, researchers will randomize a sample of adolescents with WM deficits to intermittent theta burst stimulation (iTBS) at the left dorsolateral prefrontal cortex (DLPFC) or inferior parietal lobule (IPL), based on each participant's structural brain MRI.

Participants in both arms will complete an active iTBS session and a sham iTBS session. The primary outcome will be theta-gamma coupling during WM demands, as measured via electroencephalography (EEG) during a Sternberg spatial WM task (SWMT) immediately before and after iTBS.

Group Type: EXPERIMENTAL

Active Intermittent Theta Burst Stimulation

Intervention Type: DEVICE

Standard iTBS protocol with active coil

Sham intermittent Theta Burst Stimulation

In a 2x2 factorial double-blind design, researchers will randomize a sample of adolescents with WM deficits to intermittent theta burst stimulation (iTBS) at the left dorsolateral prefrontal cortex (DLPFC) or inferior parietal lobule (IPL), based on each participant's structural brain MRI.

Participants in both arms will complete an active iTBS session and a sham iTBS session. The primary outcome will be theta-gamma coupling during WM demands, as measured via electroencephalography (EEG) during a Sternberg spatial WM task (SWMT) immediately before and after iTBS.

Group Type: EXPERIMENTAL

Sham Intermittent Theta Burst Stimulation

Intervention Type: DEVICE

Standard iTBS protocol with active coil

Interventions

Active Intermittent Theta Burst Stimulation

Standard iTBS protocol with active coil

Intervention Type: DEVICE

Sham Intermittent Theta Burst Stimulation

Standard iTBS protocol with active coil

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Ability to provide assent and have parent provide parental permission

2. English fluency of the participant and the legal guardian/parent

3. 12-18 years

4. Parent rating on BRIEF-2 Working Memory: Greater than 1.0 SD above normative mean.

5. IQ > 80

6. Clinical diagnosis of attention deficit hyperactivity disorder (ADHD): predominantly inattentive type, predominantly hyperactive/impulsive type, combined type, or unspecified type. Diagnostic criteria will be confirmed with NICHQ Vanderbilt Assessment Scales-Parent.

Exclusion Criteria

1. Intracranial pathology from a known genetic disorder (e.g., NF1, tuberous sclerosis) or from acquired neurologic disease (e.g. stroke, tumor), cerebral palsy, history of severe head injury, or significant dysmorphology

2. History of fainting spells of unknown or undetermined etiology that might constitute seizures

3. History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy

4. Any progressive (e.g., neurodegenerative) neurological disorder

5. Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)

6. Contraindicated metal implants in the head, brain or spinal cord (excluding dental implants, braces or fillings)

7. Non-removable makeup or piercings

8. Pacemaker

9. Implanted medication pump

10. Vagal nerve stimulator

11. Deep brain stimulator

12. TENS unit (unless removed completely for the study)

13. Ventriculo-peritoneal shunt

14. Signs of increased intracranial pressure

15. Intracranial lesion (including incidental finding on MRI)

16. History of head injury resulting in prolonged loss of consciousness

17. Substance abuse or dependence within past six months (i.e., DSM-5 substance use disorder criteria)

18. Chronic treatment with prescription medications that decrease cortical seizure threshold, not including psychostimulant medication if deemed to be medically safe as part of the medical review process.

19. Active psychosis or mania

20. Current suicidal intent

21. Current pregnancy

22. Significant visual, hearing or speech impairment

23. Current wards of the state

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bradley Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

E. P. Bradley Hospital

East Providence, Rhode Island, United States

Countries

United States

Other Identifiers

BradleyHK23

Identifier Type: -

Identifier Source: org_study_id