Enhancing neural markers of attention in children with ADHD using a digital therapeutic

Abstract

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by diminished attentional control. Critically, these difficulties are related to negative consequences in real-life functioning both during development and into adulthood. There is now growing evidence that modulating the underlying neural circuits related to attention can improve behavior and brain function in children with ADHD. We have previously shown that game-based digital therapeutics targeting a key neural marker of attention-midline frontal theta (MFT)-yield positive effects on attentional control in several populations. However, the effects of such digital therapeutics in children with ADHD and no other comorbidities has not been yet examined. To address this gap, we assessed a sample of 25 children with ADHD (8-12 years old) on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention on an iPad targeting MFT circuitry. We found that children showed enhancements on a neural measure of attention (MFT power), as well as on objective behavioral measures of attention and parent reports of clinical ADHD symptoms. Importantly, we observed relationships between the neural and behavioral cognitive improvements, demonstrating that those children who showed the largest intervention-related neural gains were also those that improved the most on the behavioral tasks indexing attention. These findings provide support for using targeted, digital therapeutics to enhance multiple features of attentional control in children with ADHD. Study registration: ClinicalTrials.gov registry (NCT03844269) https://ichgcp.net/clinical-trials-registry/NCT03844269.

Conflict of interest statement

JAA was paid as a consultant by Cortica to assist with study development, EEG equipment setup, neural and behavioral analysis, and manuscript preparation. EJM, MG, BC are employees of Cortica. EC is employed by Akili Interactive Labs, may own stock options, and is a patent holder (WO/2018/027080) for Processor Implemented Systems and Methods for Measuring Cognitive Abilities. Funding for this study was sponsored by Akili Interactive Labs.

Figures

Fig 1. CONSORT flow diagram.

Fig 2. Changes in primary outcome metrics: Neural markers of attention.

a Time course of midline frontal theta (MFT) pre- and post-intervention at each 40 ms time bin during the perceptual discrimination task, where 0 ms represents stimulus onset. Solid lines represent the mean and shaded areas represent 95% bootstrapped confidence intervals (1000 bootstrap iterations). b Intervention-related improvements in MFT at early, peak, and late 120 ms composite windows, also illustrated through topographic heat maps with the 6 electrodes of interest highlighted with a dotted bounding box. Data are presented as mean ± 95% bootstrapped confidence intervals (1000 bootstrap iterations), and circles represent individual participants. P-values represent repeated-measures ANOVAs comparing pre- and post-intervention MFT at each composite window.

Fig 3. Changes in exploratory outcome metrics: Behavioral and parent-report measures of attention.

Intervention-related changes in objective behavioral and parent-report measures of attention, specifically a response time (RT) on the perceptual discrimination task, b tau on the sustained attention task, and c points on the Vanderbilt inattention subscale (parent-report). Data are presented as mean ± 95% bootstrapped confidence intervals (1000 bootstrap iterations), and circles represent individual participants. d Pearson correlations between midline frontal theta (MFT) improvements at each composite window and the behavioral and parent-report improvements.