Target ADHD Executive Working Memory Study

This proposal seeks support for a 2-year milestone-driven R61 initial test of target engagement in n=62 ADHD diagnosed adolescents randomized to a 'sham training' placebo or to train 4 times each week using 4 different EWM exercises that have been combined into the format of a typical cognitive training intervention. Exercise difficulty levels in the active intervention will increase across 5 weeks to continually challenge EWM ability. EWM training will use a novel, remotely-supervised 'at home' computerized training approach. If R61 EWM training target engagement milestones are met, a 3-year R33 phase will begin. The R33 will replicate target engagement in another randomized placebo-controlled trial of n=90 new ADHD adolescents and attempt to establish a convincing link between the hypothesized targets and ADHD symptom expression. It also will characterize ADHD brain activity or EWM ability changes relative to typical levels seen in an n=40 non-ADHD control group.

• EWM Training (Behavioral): Training tasks will target Executive Working Memory areas of the brain. Task difficulty will be adaptively increased across the 5 weeks of training based on session-to-session performance.
• Placebo Training (Behavioral): Computerized tasks with comparable engagement that do not tap executive working memory processes

Primary outcomes

• Magnetic Resonance Imaging Functional Brain Scan using a Seimens 3T Skyra. [Change in fMRI measurements from baseline assessment versus 5 weeks at the conclusion of training]: fMRI measures of brain activation and functional connectivity - Conventional measures of 'brain activation' are estimated using GLM regression models that fit the fMRI BOLD timeseries data to a model of expected hemodynamic change as elicited by fMRI versions of the executive working memory training task trials. Functional connectivity is assessed using a form of cross-correlation analysis that quantifies how much the entire BOLD timeseries in different brain regions are similar to one another. Our a priori treatment target brain regions are the superior frontal sulcus and mid-lateral prefrontal cortex region of interest. Brain activity and functional connectivity specifically to these regions represent the primary outcome measures of the study.
• The experimental executive working memory training tasks [Change in scores from baseline assessment versus 5 weeks at the conclusion of training]: Will examine changes in performance accuracy on the 4 executive working memory training tasks. These are experimental, non-published tasks being tested in this project for the first time.

Sex: All, ages: 12 Years to 18 Years

Inclusion Criteria:

* Diagnosis of ADHD
* English speaking
* Right-handed
* >5th grade reading level
* >80 IQ level

Exclusion Criteria:

* Braces, metal or implant devices
* Brain abnormality, neurological disorder
* TBI or loss of consciousness>30 minutes
* Diagnosis of Psychosis, Bipolar Disorder, ASD, PTSD, OCD, SUD, Tourette's Disorder

• Informed Consent Form (PDF, 2020-11-25)

• Michael C Stevens, PhD, Principal investigator, Institute of Living/Hartford Hospital