rTMS and EF 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.


Eligibility Criteria:
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