We have studied the subjective experience of volition, rather than the objective capacity to

initiate and control voluntary action. Nevertheless, our results suggest an interesting link between subjective experience of volition and capacity for voluntary control. Voluntary control is classically thought to be unaffected in pure GTS (Ganos GSK126 datasheet et al., 2014, Ganos et al., 2013 and Jung et al., 2012), and our patients were indeed able to perform the voluntary action task successfully. However, we found a strong relation in our patients between a negative aspect of voluntary control, i.e., the capacity to suppress tics, and the capacity to experience the intentional signals preceding initiation

of voluntary action. Specifically, participants who were able to suppress their tics reported earlier experiences of volition that those who did not. Importantly, these two measures were obtained independently, in separate experimental tests – no particular instruction was given regarding tic inhibition during the voluntary action task. This result Atezolizumab suggests that the capacity to discriminate signals for volition from signals related to other involuntary movements is directly related to successful voluntary self-control. The capacity to inhibit involuntary movements could cause a stronger experience of volition, by reducing the background motor noise within which signals related to voluntary action are embedded. This would improve the landscape for perceptual learning.

However, we cannot exclude the possibility that causation might run in the opposite direction. Patients who have early experiences of volition might be better able to control voluntary suppression of other, involuntary movements that lacked this marker. Our result establishes, for the first time, an association between perception of volition, and voluntary self-control, although it cannot prove the direction of causation. Irrespective of directionality, the association between experience of volition and voluntary self-control may have important implications for Sinomenine movement disorder therapies. For example, training that focuses on perception of internal volitional signals rather than on noise related to tics could potentially increase voluntary self-control. The ability to perceive the signals associated with volition, and to discriminate them from other internal motor events, is a crucial first stage in developing the capacity for voluntary control. Humans might acquire volition using mechanisms similar to reinforcement learning of operant actions in animals (Fetz, 1969). A gradual, implicit learning process would favour motor outputs that influenced the level of a specific class of sensations, associated with drives, desires and motivations – such as reducing hunger or inducing pleasure.