Project 3

University Of California Los Angeles, Los Angeles CA

Investigators

Linked publications & trials

Abstract

A host of evidence from clinical studies and neuroimaging clearly indicates that elements of cognitive control,[unreadable] such as working memory and response inhibition, are diminished in children and adults with attention[unreadable] deficit/hyperactivity disorder. These functions are subserved in part by the fronto-striatal circuits connecting[unreadable] with dorsolateral prefrontal cortex for working memory, and with ventrolateral prefrontal cortex for response[unreadable] inhibition. Because of the known dopaminergic innervation of these areas, and the therapeutic effects of[unreadable] indirect dopaminergic agonists such as psychostimulants for ADHD, there has been interest in the direct role[unreadable] of dopamine in the modulation of the circuits underlying these abilities. Numerous studies have suggested[unreadable] that DA-modulation can yield behavioral improvements in response inhibition and WM performance in[unreadable] ADHD. Furthermore, neuroimaging work using both EEC and fMRI has suggested that DA modulation can[unreadable] result in normalized activity in children with ADHD. Pharmacologic treatment studies also suggest that other[unreadable] manipulations, such as alpha2 agonist exposure, may improve cognitive control. Our proposed studies aim[unreadable] to clarify the functional anatomy of key circuits subserving cognitive control in children and adolescents with[unreadable] ADHD and to compare and contrast hypothesized mechanisms of cognitive enhancement associated with[unreadable] dopaminergic and noradrenergic treatments in isolation or combination. Subjects recruited will undergo fMRI and EEG at Weeks 0, 4, and 8, allowing measurement of the effects of[unreadable] methylphenidate and guanfacine on behavior and neural activity. The primary aims are to determine how[unreadable] neural activity differs between children with ADHD and normal controls on response inhibition (measured[unreadable] using the stop-signal task) and spatial working memory (measured using a spatial Sternberg task)[unreadable] challenges, and how this response is modulated by pharmacotherapies. The project also aims to determine[unreadable] whether EEG and/or fMRI can predict treatment response to different pharmacotherapy regimens. These[unreadable] aims synergize with the larger Center in providing a neuroscientific basis for understanding the effects of[unreadable] treatments for developmental neuropsychiatric disorders.