This proposal addresses the neural architecture underlying how people are able to use their goals to control inappropriate urges. This has large significance for a wide range of neuropsychiatric disorders characterized by impulsivity and perseveration. In the United States, the financial and societal cost of these disorders is staggering. Better understanding how people control themselves has come from the stop- signal paradigm, in which subjects must occasionally stop an initiated response. The neural architecture underlying the form of stopping in the standard stop-signal paradigm is already quite well understood. It is highly translatable across species and it has proven a very useful biomarker for cognitive control impairments in many neuropsychiatric disorders. However, the form of stopping measured in the standard stop-signal paradigm has some limitations as a model for real world control because it appears to have global effects on the motor system. Yet a person's ability to control an inappropriate urge requires selectivity of the control (i.e. to stop one tendency but not others). We have recently proposed a new behavioral method to study selective stopping.
The first aim of this proposal is to study the neural mechanisms of selective stopping. We will use functional Magnetic Resonance Imaging (fMRI) in healthy volunteers to dissociate the fronto-basal-ganglia brain circuits for global stopping from those for selective stopping. We will use Transcranial Magnetic Stimulation (TMS) to examine the difference between global and selective stopping by identifying effects on motor representations in the primary motor cortex. We will use Electrocorticography (ECoG) in patients being evaluated for epilepsy to address how the functions of goal monitoring and response inhibition interact in the prefrontal cortex to allow a subject to stop selectively. ECoG provides unique spatiotemporal resolution to address this question in humans. Besides "stopping", real-world control also requires a form of control that prevents responding without canceling it completely -something more akin to 'braking'.
The second aim of this proposal is to study the neural mechanisms of braking and their relation with stopping. We will use all three methods of fMRI, TMS and ECoG. We anticipate that braking recruits the same brain systems as stopping, but without canceling motor output completely. Together, these studies will provide a novel neural-systems model for how selective stopping is possible and for how it relates to braking. This will enhance and expand understanding of cognitive control mechanisms, and is relevant for many diverse conditions including Obsessive Compulsive Disorder, Attention Deficit Hyperactivity Disorder, Tourette's syndrome, and substance abuse problems - all characterized by a loss of goal-driven control over particular response tendencies.

Public Health Relevance

This proposal addresses the neural architecture underlying how people are able to use their goals to control inappropriate urges. This will contribute to a better understanding of mechanisms of cognitive control. This is important for disorders such as Obsessive Compulsive Disorder, Attention Deficit Hyperactivity Disorder, Tourette's syndrome and substance abuse problems, which are all characterized by a loss of goal-driven control over particular response tendencies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA026452-05
Application #
8469843
Study Section
Cognition and Perception Study Section (CP)
Program Officer
Bjork, James M
Project Start
2009-06-15
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$299,538
Indirect Cost
$80,976
Name
University of California San Diego
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Wessel, Jan R; Aron, Adam R (2014) Inhibitory motor control based on complex stopping goals relies on the same brain network as simple stopping. Neuroimage 103:225-34
Chiu, Yu-Chin; Cools, Roshan; Aron, Adam R (2014) Opposing effects of appetitive and aversive cues on go/no-go behavior and motor excitability. J Cogn Neurosci 26:1851-60
Aron, Adam R; Robbins, Trevor W; Poldrack, Russell A (2014) Inhibition and the right inferior frontal cortex: one decade on. Trends Cogn Sci 18:177-85
Freeman, Scott M; Razhas, Ieva; Aron, Adam R (2014) Top-down response suppression mitigates action tendencies triggered by a motivating stimulus. Curr Biol 24:212-6
Chiu, Yu-Chin; Aron, Adam R (2014) Unconsciously triggered response inhibition requires an executive setting. J Exp Psychol Gen 143:56-61
Pieters, Thomas A; Conner, Christopher R; Tandon, Nitin (2013) Recursive grid partitioning on a cortical surface model: an optimized technique for the localization of implanted subdural electrodes. J Neurosurg 118:1086-97
Itthipuripat, Sirawaj; Wessel, Jan R; Aron, Adam R (2013) Frontal theta is a signature of successful working memory manipulation. Exp Brain Res 224:255-62
Majid, D S Adnan; Cai, Weidong; Corey-Bloom, Jody et al. (2013) Proactive selective response suppression is implemented via the basal ganglia. J Neurosci 33:13259-69
Wessel, Jan R; Reynoso, H Sequoyah; Aron, Adam R (2013) Saccade suppression exerts global effects on the motor system. J Neurophysiol 110:883-90
Greenhouse, Ian; Oldenkamp, Caitlin L; Aron, Adam R (2012) Stopping a response has global or nonglobal effects on the motor system depending on preparation. J Neurophysiol 107:384-92

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