rTMS and EF Training for Working Memory Deficits in Adolescent Psychopathology

rTMS and Executive Functioning Training for Working Memory Deficits in Adolescent Psychopathology

Executive functioning (EF) deficits are a core, transdiagnostic feature of psychopathology and one of the strongest predictors of clinical and functional outcomes, yet there remains a dearth of treatments available for EF deficits. EF is a collection of cognitive control processes that includes working memory (i.e., maintain/manipulate data not perceptually present), inhibition (i.e., inhibit/control of attention, thoughts, behaviors) and flexibility (i.e., shift flexibly between tasks/sets). These EF subdomains are subserved by a network (i.e., cognitive control network) of frontal (e.g., dorsolateral prefrontal cortex [DLPFC]), parietal and subcortical regions, with hypoactivation in such regions often underlying EF deficits. There is a recent call in psychiatry to develop experimental therapeutics that target anomalous neural systems underlying symptomology. Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic, non-invasive method of cortical excitability modulation. High frequency rTMS to the left DPLFC has an activating effect on the cognitive control network, with initial research in adults finding a subsequent enhancing effect on working memory, inhibition, and flexibility. rTMS represents a very promising potential tool to target EF deficits in psychopathology.

Study Overview

• Status: Unknown
• Conditions: ADHD With Working Memory Deficits
• Intervention / Treatment: Device: Magstim Super Rapid2 stimulator, 10 Hz condition; Device: Magstim Super Rapid2 stimulator, Sham condition; Device: Magstim Super Rapid2 stimulator, iTBS condition

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brian Kavanaugh, PsyD; Phone Number: 401 432 1359; Email: brian_Kavanaugh@brown.edu
• Study Contact Backup: Name: Anthony Spirito, PhD; Email: Anthony_Spirito@Brown.edu

Study Locations

• United States
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Recruiting
      • E. P. Bradley Hospital
      • Contact: Brian Kavanaugh, PsyD; Phone Number: 401-432-1359; Email: Brian_Kavanaugh@Brown.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to provide assent and have parent provide parental permission
2. English fluency
3. 13-17 years
4. List Sorting Test (NIH Toolbox) performance: Greater than 1.0 standard deviation (SD) below normative mean
5. Parent rating on BRIEF-2 Working Memory: Greater than 1.0 SD above normative mean
6. IQ > 80
7. 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:

Participants will be screened to exclude individuals with neurological or medical conditions that might confound the results, as well as to exclude participants in whom rTMS might result in increased risk of side effects or complications. Common TMS contraindications include metallic hardware in the body, cardiac pacemaker, patients with an implanted medication pumps or an intracardiac line, or prescription of medications known to lower seizure threshold. This accounts for the majority of the exclusion criteria listed:

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 or fillings)
7. Pacemaker
8. Implanted medication pump
9. Vagal nerve stimulator
10. Deep brain stimulator
11. TENS unit (unless removed completely for the study)
12. Ventriculo-peritoneal shunt
13. Signs of increased intracranial pressure
14. Intracranial lesion (including incidental finding on MRI)
15. History of head injury resulting in prolonged loss of consciousness
16. Substance abuse or dependence within past six months (i.e., DSM-5 substance use disorder criteria met)
17. Chronic treatment with prescription medications that decrease cortical seizure threshold

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham rTMS	Device: Magstim Super Rapid2 stimulator, Sham condition; sham
Experimental: 10 Hz rTMS	Device: Magstim Super Rapid2 stimulator, 10 Hz condition; 10 Hz (2,000 pulses) at left DLPFC
Experimental: iTBS rTMS	Device: Magstim Super Rapid2 stimulator, iTBS condition; 50 Hz, iTBS (600 pulses) at left DLPFC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compared to sham condition, activation of the left DLPFC prior to EF training will temporarily increase working memory performance as measured by the Sternberg Spatial Working Memory Test	The SWMT is a performance-based neuropsychological test of working memory	Task performance will be measured immediately prior to and following the active and sham rTMS/EF training sessions.

Secondary Outcome Measures

Outcome Measure	Time Frame
Compared to sham condition, activation of the left DLPFC prior to EF training will temporarily increase fronto-parietal gamma power and theta-gamma coupling during working memory demands.	EEG will be measured during SWMT immediately prior to and following the active and sham rTMS/EF training sessions.

Collaborators and Investigators

• Sponsor: Bradley Hospital
• Collaborators: Thrasher Research Fund; Rhode Island Foundation
• Investigators: Principal Investigator: Brian Kavanaugh, PsyD, E. P. Bradley Hospital/Alpert Medical School of Brown University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Anticipated): January 30, 2021
• Study Completion (Anticipated): March 30, 2021

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: March 26, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): November 14, 2019
• Last Update Submitted That Met QC Criteria: November 12, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Memory Disorders
• Other Study ID Numbers: BradleyH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No