Translational Research to Enhance Cognitive Control

University Of California Los Angeles, Los Angeles CA

Investigators

Linked publications & trials

Abstract

Although current medication therapies ameliorate ADHD behavioral symptoms, problems with inadequate[unreadable] response or tolerability are common. Most perplexing, in consideration of ADHD-related cognitive deficits[unreadable] and in spite of several hundred studies demonstrating acute behavioral response to stimulants, is the failure[unreadable] of many decades of research to demonstrate long-term, stimulated-related enhancements in learning. This[unreadable] manifest inadequacy of current therapies highlights the potential importance of developing treatments that[unreadable] specifically remediate executive function deficits as an important path to improve outcome.[unreadable] Neurochemical influences on cognitive functions in ADHD are complex. The over-arching premise of this[unreadable] project is that optimal behavioral and cognitive responses are possible with treatments that robustly enhance[unreadable] both dopamine (DA) and norepinephrine (NE). Our goal is to test the short-term efficacy of a combination[unreadable] pharmacotherapy, derived from translational research and clinical observations, against standard stimulant[unreadable] monotherapy on both symptom and cognitive endpoints. In addition, a novel aspect of the study will be to[unreadable] test prospectively whether a dual benefit on both behavior and cognition predicts clinically significant[unreadable] improvements in learning over longer-term treatment. Lastly, based upon our preliminary data and[unreadable] hypothesized mechanisms of treatment response, the proposed study will examine the potential of[unreadable] electroencephalography (EEC) in predicting optimal long-term benefit. The clinical trial will enroll 180[unreadable] children and adolescents with ADHD-Combined Type in an active-controlled randomized parallel group study[unreadable] testing the comparative efficacy of guanfacine (GUAN), methylphenidate (MPH), and combination[unreadable] GUAN/MPH on ADHD symptoms and clinical response rates. Improvements in cognition during the acute[unreadable] treatment phase will predict greater academic achievement over the 12 month maintenance period.[unreadable] The project will represent an initial scientific investment in a new phase of translational treatment research[unreadable] on cognition in developmental psychopathologies. The designs and methodology tested in the proposed trial[unreadable] will serve as a platform for testing other interventions.