Modulation of Frontoparietal Dynamics Underlying Adolescent Working Memory Deficits

NCT ID: NCT05119660

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2024-03-30

Brief Summary

The purpose of this study is to test whether a single session of brain stimulation (called repetitive transcranial magnetic stimulation [rTMS]) can improve the brain activity underlying 'working memory.' Working memory is the ability to hold information 'in mind' to complete daily activities. This study involves teenagers with ADHD as well as healthy young adults. It is funded by The COBRE Center for Neuromodulation (CCN) at Butler Hospital (Pilot Project)

Detailed Description

The objective of this project is to examine the contributing roles of the PPC and PFC in WM processes and relatedly, develop optimal targets for modulating WM-related neural oscillations. Patient Arm: In a 2x2 factorial double-blind design, we will randomize a sample of adolescents (13-18 years) 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. Control Arm: A sample of healthy young adults (18-25 years) will receive an individualized theta-gamma parameters protocol of iTBS to the left DLPFC. 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. The 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. Our central hypothesis is formulated based on our preliminary data on the critical role of theta-gamma coupling in WM processes. To attain the overall objectives, the following specific aims will be pursued:

Aim 1: Examine the effect of iTBS to the PPC on the encoding stage of WM. Hypothesis: Compared to sham and DLPFC conditions, iTBS to the IPL will increase theta-gamma coupling during encoding. Modulation of theta-gamma coupling will correlate with improved behavioral performance.

Aim 2: Examine the effect of iTBS to the PFC on the maintenance stage of WM. Hypothesis: Compared to sham and IPL conditions, iTBS to the DLPFC will increase theta-gamma coupling during maintenance. Modulation of theta-gamma coupling will correlate with improved behavioral performance.

Aim 3: Examine the feasibility and preliminary effect of individualized iTBS to the PFC. Hypothesis: It will be feasible to utilize peak theta-gamma coupling during the SWMT to identify optimal iTBS parameters. Individualized iTBS will increase theta-gamma coupling during WM demands and improve behavioral performance.

Exploratory Aim: Identify the neocortical circuitry underlying oscillatory modulation. Computational modeling designed for neural interpretation of EEG will translate obtained recordings into cellular/circuit-level activity delineating the neural mechanism of the observed modulation. Hypothesis: pyramidal-interneuron mechanisms within the PPC/PFC will underlie the theta/gamma oscillatory modulation.

Conditions

ADHD

Study Design

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

Study Groups

Patient Arm

In a 2x2 factorial double-blind design, we will randomize a sample of adolescents (13-18 years) 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

Intermittent Theta Burst Stimulation

Intervention Type: DEVICE

iTBS

Healthy Control Arm

Control Arm: A sample of healthy young adults (18-25 years) will receive an individualized theta-gamma parameters protocol of iTBS to the left DLPFC.

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

Intermittent Theta Burst Stimulation

Intervention Type: DEVICE

iTBS

Interventions

Intermittent Theta Burst Stimulation

iTBS

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. 13-18 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.

1. Ability to provide consent

2. English fluency of the participant

3. 18-25 years

4. Never diagnosed or meets current criteria for a psychiatric disorder, as measured by self-report of prior diagnoses and formal completion of the diagnostic interview.

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: 13 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Funding Source: COBRE Center for Neuromodulation at Butler Hospital (Pilot Project)

UNKNOWN

Sponsor Role: collaborator

Bradley Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

E. P. Bradley Hospital

East Providence, Rhode Island, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Brian C Kavanaugh, PsyD ABPP

Role: CONTACT

Bkavanaugh@Lifespan.org

401 432 1359

Facility Contacts

Brian C Kavanaugh, PsyD ABPP

Role: primary

Bkavanaugh@lifespan.org

401-432-1359

Other Identifiers

BradleyH002

Identifier Type: -

Identifier Source: org_study_id