Learning motor tasks involves distinct physiological processes in the cerebellum (CB) and primary motor cortex (M1). Previous studies have shown that motor learning results in at least two important ...neurophysiological changes: modulation of cerebellar output mediated in-part by long-term depression of parallel fiber-Purkinje cell synapse and induction of long-term plasticity (LTP) in M1, leading to transient occlusion of additional LTP-like plasticity. However, little is known about the temporal dynamics of these two physiological mechanisms during motor skill learning. Here we use non-invasive brain stimulation to explore CB and M1 mechanisms during early and late motor skill learning in humans. We predicted that early skill acquisition would be proportional to cerebellar excitability (CBI) changes, whereas later stages of learning will result in M1 LTP-like plasticity modifications. We found that early, and not late into skill training, CBI changed. Whereas, occlusion of LTP-like plasticity over M1 occurred only during late, but not early training. These findings indicate a distinct temporal dissociation in the physiological role of the CB and M1 when learning a novel skill. Understanding the role and temporal dynamics of different brain regions during motor learning is critical to device optimal interventions to augment learning.
Highlights • A review of technical aspects of transcranial electrical stimulation (tES) techniques. • Recommendations for safe and replicable application of tDCS and other tES methods. • Discussion ...of state-of-the-art methodology and design considerations in tES.
Adaptation to a novel visuomotor transformation has revealed important principles regarding learning and memory. Computational and behavioral studies have suggested that acquisition and retention of ...a new visuomotor transformation are distinct processes. However, this dissociation has never been clearly shown. Here, participants made fast reaching movements while unexpectedly a 30-degree visuomotor transformation was introduced. During visuomotor adaptation, subjects received cerebellar, primary motor cortex (M1) or sham anodal transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation known to increase excitability. We found that cerebellar tDCS caused faster adaptation to the visuomotor transformation, as shown by a rapid reduction of movement errors. These findings were not present with similar modulation of visual cortex excitability. In contrast, tDCS over M1 did not affect adaptation, but resulted in a marked increase in retention of the newly learnt visuomotor transformation. These results show a clear dissociation in the processes of acquisition and retention during adaptive motor learning and demonstrate that the cerebellum and primary motor cortex have distinct functional roles. Furthermore, they show that is possible to enhance cerebellar function using tDCS.
Plasticity of synaptic connections in the primary motor cortex (M1) is thought to play an essential role in learning and memory. Human and animal studies have shown that motor learning results in ...long-term potentiation (LTP)-like plasticity processes, namely potentiation of M1 and a temporary occlusion of additional LTP-like plasticity. Moreover, biochemical processes essential for LTP are also crucial for certain types of motor learning and memory. Thus, it has been speculated that the occlusion of LTP-like plasticity after learning, indicative of how much LTP was used to learn, is essential for retention. Here we provide supporting evidence of it in humans. Induction of LTP-like plasticity can be abolished using a depotentiation protocol (DePo) consisting of brief continuous theta burst stimulation. We used transcranial magnetic stimulation to assess whether application of DePo over M1 after motor learning affected (1) occlusion of LTP-like plasticity and (2) retention of motor skill learning. We found that the magnitude of motor memory retention is proportional to the magnitude of occlusion of LTP-like plasticity. Moreover, DePo stimulation over M1, but not over a control site, reversed the occlusion of LTP-like plasticity induced by motor learning and disrupted skill retention relative to control subjects. Altogether, these results provide evidence of a link between occlusion of LTP-like plasticity and retention and that this measure could be used as a biomarker to predict retention. Importantly, attempts to reverse the occlusion of LTP-like plasticity after motor learning comes with the cost of reducing retention of motor learning.
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.
The cerebellum is a crucial structure involved in motor control and learning processes. Although imaging and studies in patients with cerebellar disease have helped understand the cerebellar role in ...different motor behaviors, little is known about the neurophysiological changes occurring in the cerebellum during human motor learning. In this talk, I will present a series of recent studies that assessed cerebellar neurophysiological contributions to learning and how manipulation of cerebellar excitability affects motor learning processes. First, I will describe how cerebellar excitability is specifically modulated in association to motor learning. Then, I will show that it is possible to modulate cerebellar excitability in humans using transcranial direct current stimulation (tDCS). Finally, I will present 2 studies that found that enhancing cerebellar excitability with anodal tDCS improves learning of a hand and a locomotor behavior. These investigations indicate that it is possible to determine neurophysiological processes underlying behaviors that involve the cerebellum, that we can up-and down-regulate cerebellar excitability using non-invasive brain stimulation techniques, and that this modulation has an impact in behavior. These results are promising not only to advance our understanding of the role of the cerebellum in motor control, but also to develop strategies to enhance performance, learning and possibly recovery in patients with brain lesions.
Motor practice is associated with the formation of elementary motor memories. Here we tested in human subjects the hypothesis that observation of a motor training associated with physical practice ...will modulate the encoding process of a motor memory relative to physical practice alone. Voluntary thumb motions were practiced (i) alone in a direction opposite to the baseline direction of transcranial magnetic stimulation (TMS)‐evoked movements (physical practice, PP) and in combination with observation of synchronous movements that were either (ii) directionally congruent (same direction, PP + AOc) or (iii) non‐congruent (opposite direction, PP + AOnc) to the practiced ones. We evaluated the following measures of motor memory formation: percentage of TMS‐evoked thumb movements falling in the direction of practiced motions, acceleration of TMS‐evoked movements along the principal movement axis and corticomuscular excitability of training muscles as indexed by motor‐evoked potential amplitudes. Both PP and PP + AOc, but not PP + AOnc, significantly increased the percentage of TMS‐evoked movements falling in the practiced direction, changed the compound acceleration vector into the trained direction and enhanced the motor‐evoked potential amplitudes in the training agonist muscle. The percentage of TMS‐evoked movements falling in the practiced direction increased significantly more after PP + AOc than after PP. Across all measures of motor memory formation, PP + AOc was most efficacious, followed by PP and PP + AOnc. Action observation modulates practice effects on formation of a motor memory. Strengthening of the process of motor memory encoding depends on the directional congruency of the observed model.
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