The cerebellum is a crucial structure involved in movement control and cognitive processing. Noninvasive stimulation of the cerebellum results in neurophysiological and behavioral changes, an effect that has been attributed to modulation of cerebello-brain connectivity. At rest, the cerebellum exerts an overall inhibitory tone over the primary motor cortex (M1), cerebello-brain inhibition (CBI), likely through dentate-thalamo-cortical connections. The level of excitability of this pathway before and after stimulation of the cerebellum, however, has not been directly investigated. In this study, we used transcranial magnetic stimulation to determine changes in M1, brainstem, and CBI before and after 25 min of anodal, cathodal, or sham transcranial direct current stimulation (tDCS) applied over the right cerebellar cortex. We hypothesized that anodal tDCS would result in an enhancement of CBI and cathodal would decrease it, relative to sham stimulation. We found that cathodal tDCS resulted in a clear decrease of CBI, whereas anodal tDCS increased it, in the absence of changes after sham stimulation. These effects were specific to the cerebello-cortical connections with no changes in other M1 or brainstem excitability measures. The cathodal effect on CBI was found to be dependent on stimulation intensity and lasted up to 30 min after the cessation of tDCS. These results suggest that tDCS can modulate in a focal and polarity-specific manner cerebellar excitability, likely through changes in Purkinje cell activity. Therefore, direct current stimulation of the cerebellum may have significant potential implications for patients with cerebellar dysfunction as well as to motor control studies.

Research highlights► Transcranial direct current stimulation (tDCS) modulates explicit sequence learning. ► Anodal tDCS applied during the task speeds motor learning. ► Anodal tDCS applied before the task slows motor learning. ► Cathodal tDCS slows the rate of learning in both cases.

Human locomotor adaptation is necessary to maintain flexibility of walking. Several lines of research suggest that the cerebellum plays a critical role in motor adaptation. In this study we investigated the effects of noninvasive stimulation of the cerebellum to enhance locomotor adaptation. We found that anodal cerebellar transcranial direct current stimulation (tDCS) applied during adaptation expedited the adaptive process while cathodal cerebellar tDCS slowed it down, without affecting the rate of de-adaptation of the new locomotor pattern. Interestingly, cerebellar tDCS affected the adaptation rate of spatial but not temporal elements of walking. It may be that spatial and temporal control mechanisms are accessible through different neural circuits. Our results suggest that tDCS could be used as a tool to modulate locomotor training in neurological patients with gait impairments.

Human locomotor adaptive learning is thought to involve the cerebellum, but the neurophysiological mechanisms underlying this process are not known. While animal research has pointed to depressive modulation of cerebellar outputs, a direct correlation between adaptive learning and cerebellar depression has never been demonstrated. Here, we used transcranial magnetic stimulation to assess excitability changes occurring in the cerebellum and primary motor cortex (M1) after individuals learned a new locomotor pattern on a split-belt treadmill. To control for potential changes associated to task performance complexity, the same group of subjects was also assessed after performing 2 other locomotor tasks that did not elicit learning. We found that only adaptive learning resulted in reduction of cerebellar inhibition. This effect was strongly correlated with the magnitude of learning (r = 0.78). In contrast, M1 excitability changes were not specific to learning but rather occurred in association with task complexity performance. Our results demonstrate that locomotor adaptive learning in humans is proportional to cerebellar excitability depression. This finding supports the theory that adaptive learning is mediated, at least in part, by long-term depression in Purkinje cells. This knowledge opens the opportunity to target cerebellar processes with noninvasive brain stimulation to enhance motor learning.