Canceling a pending movement is a hallmark of voluntary behavioral control because it allows us to quickly adapt to unattended changes either in the external environment or in our thoughts. The countermanding paradigm allows the study of inhibitory processes of motor acts by requiring the subject to withhold planned movements in response to an infrequent stop-signal. At present the neural processes underlying the inhibitory control of arm movements are mostly unknown. We recorded the activity of single units in the rostral and caudal portion of the dorsal premotor cortex (PMd) of monkeys trained in a countermanding reaching task. We found that among neurons with a movement-preparatory activity, about one-third exhibit a modulation before the behavioral estimate of the time it takes to cancel a planned movement. Hence these neurons exhibit a pattern of activity suggesting that PMd plays a critical role in the brain networks involved in the control of arm movement initiation and suppression.

The precise localizations of the neural substrates of voluntary inhibition are still debated. It has been hypothesized that, in humans, this executive function relies upon a right-lateralized pathway comprising the inferior frontal gyrus and the presupplementary motor area, which would control the neural processes for movement inhibition acting through the right subthalamic nucleus (STN). We assessed the role of the right STN, via a countermanding reaching task, in 10 Parkinson’s patients receiving high-frequency electrical stimulation of the STN of both hemispheres (deep brain stimulation, DBS) and in 13 healthy subjects. We compared the performance of Parkinson’s patients in 4 experimental conditions: DBS-ON, DBS-OFF, DBS-OFF right, and DBS-OFF left. We found that 1) inhibitory control is improved only when both DBS are active, that is, the reaction time to the stop signal is significantly shorter in the DBS-ON condition than in all the others, 2) bilateral stimulation of STN restores the inhibitory control to a near-normal level, and 3) DBS does not cause a general improvement in task-related motor function as it does not affect the length of the reaction times of arm movements, that is, in our experimental context, STN seems to play a selective role in response inhibition.

All actions, even the simplest like moving an arm to grasp a pen, are associated with energy costs. Thus all mobile organisms possess the ability to evaluate resources and select those behaviours that are most likely to lead to the greatest accrual of valuable items (rewards) in the near or, especially in the case of humans, distant future. The evaluation process is performed at all possible stages of the series of decisions that lead to the building of a goal-directed action or to its suppression. This is because all animals have a limited amount of energy and resources; to survive and be able to reproduce they have to minimize the costs and maximize the outcomes of their actions. These computations are at the root of behavioral flexibility. Two executive functions play a major role in generating flexible behaviors: i) the ability to predict future outcomes of goal-directed actions; and ii) the ability to cancel them when they are unlikely to accomplish valuable results. These two processes operate continuously during the entire course of a movement: during its genesis, its planning and even its execution, so that the motor output can be modulated or suppressed at any time before its execution. In this review, functional interactions of the extended neural network subserving generation and inhibition of goal-directed movements will be outlined, leading to the intriguing hypothesis that the performance of actions and their suppression are not specified by independent sets of brain regions. Rather, it will be proposed that acting and stopping are functions emerging from specific interactions between largely overlapping brain regions, whose activity is intimately linked (directly or indirectly) to the evaluations of pros and cons of an action. Such mechanism would allow the brain to perform as a highly efficient and flexible system, as different functions could be computed exploiting the same components operating in different configurations.

Cognitive functions like motor planning rely on the concerted activity of multiple neuronal assemblies underlying still elusive computational strategies. During reaching tasks, we observed stereotyped sudden transitions (STs) between low and high multiunit activity of monkey dorsal premotor cortex (PMd) predicting forthcoming actions on a single-trial basis. Occurrence of STs was observed even when movement was delayed or successfully canceled after a stop signal, excluding a mere substrate of the motor execution. An attractor model accounts for upward STs and high-frequency modulations of field potentials, indicative of local synaptic reverberation. We found in vivo compelling evidence that motor plans in PMd emerge from the coactivation of such attractor modules, heterogeneous in the strength of local synaptic self-excitation. Modules with strong coupling early reacted with variable times to weak inputs, priming a chain reaction of both upward and downward STs in other modules. Such web of “flip-flops” rapidly converged to a stereotyped distributed representation of the motor program, as prescribed by the long-standing theory of associative networks.