This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The development of functional magnetic resonance imaging (fMRI) techniques has revolutionized the study of human cognition by spatially and temporally isolating brain activity related to specific processes, such as alerting and the inhibitory control of behavior. Alerting refers to the capacity to phasically increase readiness to detect and respond to an impending stimulus, while inhibitory control is a self-regulatory function that encompasses the directed suppression of inappropriate response tendencies and interference. These processes are critical for the adaptation of responses to context and the maintenance of goal-directed behavior, and deficits in both alerting and inhibitory control have been found in several disorders, including attention-deficit/hyperactivity disorder (ADHD). Research with fMRI has already identified several brain regions involved in alerting and inhibitory control processes. Studies have consistently reported activation of a neural network distributed across the ventral prefrontal cortex, supplementary motor area, and possibly basal ganglia during a range of inhibitory control tasks. In contrast, phasic increases in alerting have been associated with bilateral activation of thalamic nuclei and the inferior and superior parietal lobules. However, nearly of all these studies also reported activation of anterior cingulate gyrus and other brain regions that are involved in motor control and mnemonic functions, and which are more commonly associated with responding than alerting or inhibition. These common regions of activation highlight the limitations of current paradigms designed to test inhibitory control and alerting, including not adequately controlling for motor activity and other potentially confounding processes. These limitations have particular impact on the interpretation of significant differences in activation between clinical populations and controls, and highlight the constant need for task development and improvement in fMRI research. We have developed two new tasks to test alerting and inhibitory control processes that control for the confounding factors identified in previous studies. These tasks are currently being validated in a sample of college students and will be used to test young adults with childhood ADHD in pending K01 (1 K01 MH070892-01A1; P.I.: Schulz) and R01 proposals (2 RO1 MH060698-06; P.I.: Halperin). However, the Stay Alert! and Sinai Go/No-Go tasks must be tested in the MRI scanner with healthy volunteers before they can be used with clinical populations. Hypotheses: 1. Participants will respond more rapidly to target stimuli that are preceded by cues than target stimuli that are not cued in the Stay Alert! task. Further, the cues in the task will produce robust, bilateral activation of the thalamus, as well as the inferior and superior parietal lobules when compared to noncues. 2. Successful response inhibition on the Go/No-Go task will be associated with increased activation of the ventrolateral prefrontal cortex, supplementary motor area, and basal gangli
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