Enhancing transdiagnostic mechanisms of cognitive dyscontrol using computer-based training

Mood, anxiety, and traumatic stress disorders are common psychiatric conditions - affecting over 40 million U.S.
adults - and are leading causes of disability worldwide. People with these conditions are commonly plagued by
difficulty controlling distressing personal thoughts and memories, collectively referred to as repetitive negative
thinking symptoms. Models suggest that repetitive negative thinking is driven by executive functioning deficits,
such that cognitive resources are insufficient to downregulate unwanted thoughts. Executive functioning deficits
could be a promising treatment target but are not typically addressed with existing interventions. The long-term
goal advanced by this proposal is to develop effective, mechanistic cognitive training programs that can improve
cognition and reduce symptoms associated with mood, anxiety, and traumatic stress disorders. The objectives
of this proposal are first to determine the optimal dose of a cognitive training program designed to improve
executive functioning in this population using behavioral and neural outcomes (R61). If the cognitive training
tested in the R61 successfully improves executive functioning (go/no-go decision), we will evaluate the
relationship between change in executive functioning and change in clinical symptoms (R33). Our central
hypothesis is that repeated training exercises will enhance executive functioning and will lead to a reduction of
repetitive negative thinking in mood, anxiety, and traumatic stress disorders. The hypothesis will be tested by
pursing two specific aims: Aim 1 is to identify the cognitive effects and optimal dose of cognitive training. Aim 2
is to evaluate the clinical effects of the optimized cognitive training program relative to a sham condition. We will
also conduct an exploratory aim to determine generalization of cognitive training to real-world cognitive
performance. The R61 phase will test Aim 1 by randomizing participants with depression, anxiety, and/or
traumatic stress disorders to one of two doses of cognitive training or a no-treatment control condition. We will
examine executive functioning change with cognitive task performance and functional neuroimaging
assessments. The R33 phase will randomize participants to the dose decided by the R61 or a sham condition.
The R33 intends to replicate the impact on executive functioning and assess the relationship between change
in executive functioning and clinical symptoms. We will explore how cognitive training helps people in their daily
lives by including assessments given with a smartphone mobile cognitive testing app. The research proposed is
innovative because it aims to address symptoms by intervening on a cognitive target thought to generate
symptoms across multiple disorders, thus explicitly testing the interactions of cognitive and emotional symptoms.
Outcomes derived from the proposed research will include a novel treatment program and information about its
utility for reducing clinical symptoms. Knowledge from this proposal will advance our treatment options by
targeting a specific cognitive system, providing a foundation for neuroscience-based therapeutic alternative for
symptoms that span mood, anxiety, and traumatic stress disorders.

Grant Number: 5R33MH127005-04
NIH Institute/Center: NIH
Principal Investigator: Jessica Bomyea