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J Neurosci. 2014 Feb 26;34(9):3210-7. doi: 10.1523/JNEUROSCI.4081-13.2014.

Motivational tuning of fronto-subthalamic connectivity facilitates control of action impulses.

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Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, 2650 Hvidovre, Denmark, Department of Neuroscience and Pharmacology and Department of Nutrition, Exercise, and Sports, University of Copenhagen, 2200 Copenhagen, Denmark, Department of Psychology and Cognitive Science Center Amsterdam, University of Amsterdam, 1018 Amsterdam, The Netherlands, DTU Informatics, Technical University of Denmark, 2800 Lyngby, Denmark, Department of Neurology, Copenhagen University Hospital Bispebjerg, 2400 Copenhagen, Denmark, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.


It is critical for survival to quickly respond to environmental stimuli with the most appropriate action. This task becomes most challenging when response tendencies induced by relevant and irrelevant stimulus features are in conflict, and have to be resolved in real time. Inputs from the pre-supplementary motor area (pre-SMA) and inferior frontal gyrus (IFG) to the subthalamic nucleus (STN) are thought to support this function, but the connectivity and causality of these regions in calibrating motor control has not been delineated. In this study, we combined off-line noninvasive brain stimulation and functional magnetic resonance imaging, while young healthy human participants performed a modified version of the Simon task. We show that impairing pre-SMA function by noninvasive brain stimulation improved control over impulsive response tendencies, but only when participants were explicitly rewarded for fast and accurate responses. These effects were mediated by enhanced activation and connectivity of the IFG-STN pathway. These results provide causal evidence for a pivotal role of the IFG-STN pathway during action control. Additionally, they suggest a parallel rather than hierarchical organization of the pre-SMA-STN and IFG-STN pathways, since interruption of pre-SMA function can enhance IFG-STN connectivity and improve control over inappropriate responses.


Simon task; TMS; fMRI; motor control; pre-SMA; reward

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