RT Journal Article SR Electronic T1 Variability of Human Corticospinal Excitability Tracks the State of Action Preparation JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5564 OP 5572 DO 10.1523/JNEUROSCI.2448-12.2013 VO 33 IS 13 A1 Klein-Flügge, Miriam C. A1 Nobbs, David A1 Pitcher, Julia B. A1 Bestmann, Sven YR 2013 UL http://www.jneurosci.org/content/33/13/5564.abstract AB Task-evoked trial-by-trial variability is a ubiquitous property of neural responses, yet its functional role remains largely unclear. Recent work in nonhuman primates shows that the temporal structure of neural variability in several brain regions is task-related. For example, trial-by-trial variability in premotor cortex tracks motor preparation with increasingly consistent firing rates and thus a decline in variability before movement onset. However, whether noninvasive measures of the variability of population activity available from humans can similarly track the preparation of actions remains unknown. We tested this by using single-pulse transcranial magnetic stimulation (TMS) over primary motor cortex (M1) to measure corticospinal excitability (CSE) at different times during action preparation. First, we established the basic properties of intrinsic CSE variability at rest. Then, during the task, responses (left or right button presses) were either directly instructed (forced choice) or resulted from a value decision (choice). Before movement onset, we observed a temporally specific task-related decline in CSE variability contralateral to the responding hand. This decline was stronger in fast-response compared with slow-response trials, consistent with data in nonhuman primates. For the nonresponding hand, CSE variability also decreased, but only in choice trials, and earlier compared with the responding hand, possibly reflecting choice-specific suppression of unselected actions. These findings suggest that human CSE variability measured by TMS over M1 tracks the state of motor preparation, and may reflect the optimization of preparatory population activity. This provides novel avenues in humans to assess the dynamics of action preparation but also more complex processes, such as choice-to-action transformations.