Modulation of cerebellar excitability by polarity-specific noninvasive direct current stimulation

The cerebellum is a crucial structure involved in movement control and cognitive processing. Non-invasive 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 (TMS) to determine changes in M1, brainstem and CBI before and after 25 minutes 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 minutes 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

Effects of brain polarization on reaction times and pinch force in chronic stroke

BACKGROUND: Previous studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1(affected hemisphere)) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design. RESULTS: Anodal tDCS shortened reaction times and improved pinch force in the paretic hand relative to Sham stimulation, an effect present in patients with higher impairment. CONCLUSION: tDCS of M1(affected hemisphere )can modulate performance of motor tasks simpler than those previously studied, a finding that could potentially benefit patients with relatively higher impairment levels

Human locomotor adaptive learning is proportional to depression of cerebellar excitability

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

Dynamic modulation of cerebellar excitability for abrupt, but not gradual, visuomotor adaptation

The cerebellum is critically important for error driven adaptive motor learning, as evidenced by the fact that cerebellar patients do not adapt well to sudden predictable perturbations. However, recent work has shown that cerebellar patients adapt much better if the perturbation is gradually introduced. Here we explore physiological mechanisms that underlie this distinction between abrupt and gradual motor adaptation in humans. We used Transcranial Magnetic Stimulation (TMS) to evaluate whether neural mechanisms within the cerebellum contribute to either process during a visuomotor reach adaptation. When a visuomotor rotation was introduced abruptly, cerebellar excitability changed early in learning, and approached baseline levels near the end of the adaptation block. However, we observed no modulation of cerebellar excitability when we presented the visuomotor rotation gradually during learning. Similarly, we did not observe cerebellar modulation during trial-by-trial adaptation to random visuomotor displacements or during reaches without perturbations. This suggests that the cerebellum is most active during the early-phases of adaptation when large perturbations are successfully compensated

Disrupting the ventral premotor cortex interferes with the contribution of action observation to use-dependent plasticity

Action observation (AO), observing another individual perform an action, has been implicated in several higher cognitive processes including forming basic motor memories. Previous work has shown that physical practice (PP) results in cortical motor representational changes, referred to as use-dependent plasticity (UDP), and that AO combined with PP potentiates UDP in both healthy adults and stroke patients. In humans, AO results in activation of the ventral premotor cortex (PMv), however, whether PMv activation has a functional contribution to UDP is not known. Here, we studied the effects disruption of PMv has on UDP when subjects performed PP combined with AO (PP+AO). Subjects participated in 2 randomized-crossover sessions measuring the amount of UDP resulting from PP+AO while receiving disruptive (1Hz) transcranial magnetic stimulation (TMS) over the fMRI activated PMv or over orbito-frontal cortex (FC, Sham). We found that unlike the sham session, disruptive TMS over PMv reduced the beneficial contribution of AO to UDP. To ensure that disruption of PMv was specifically interfering with the contribution of AO and not PP, subjects completed two more control sessions where they performed only PP while receiving disruptive TMS over PMv or FC. We found that the magnitude of UDP for both control sessions was similar to PP+AO with TMS over PMv. These findings suggest that the fMRI activation found in PMv during action observation studies is functionally relevant to task performance, at least for the beneficial effects that AO exerts over motor training

Cerebellar tDCS: A Novel Approach to Augment Language Treatment Post-stroke

People with post-stroke aphasia may have some degree of chronic deficit for which current rehabilitative treatments are variably effective. Accumulating evidence suggests that transcranial direct current stimulation (tDCS) may be useful for enhancing the effects of behavioral aphasia treatment. However, it remains unclear which brain regions should be stimulated to optimize effects on language recovery. Here, we report on the therapeutic potential of right cerebellar tDCS in augmenting language recovery in SMY, who sustained bilateral MCA infarct resulting in aphasia and anarthria. We investigated the effects of 15 sessions of anodal cerebellar tDCS coupled with spelling therapy using a randomized, double-blind, sham controlled within-subject crossover trial. We also investigated changes in functional connectivity using resting state functional magnetic resonance imaging before and 2 months post-treatment. Both anodal and sham treatments resulted in improved spelling to dictation for trained and untrained words immediately after and 2 months post-treatment. However, there was greater improvement with tDCS than with sham, especially for untrained words. Further, generalization to written picture naming was only noted during tDCS but not with sham. The resting state functional connectivity data indicate that improvement in spelling was accompanied by an increase in cerebro-cerebellar network connectivity. These results highlight the therapeutic potential of right cerebellar tDCS to augment spelling therapy in an individual with large bilateral chronic strokes

No evidence for motor-recovery-related cortical connectivity changes after stroke using resting-state fMRI

It has been proposed that a form of cortical reorganization (changes in functional connectivity between brain areas) can be assessed with resting-state (rs) functional MRI (fMRI). Here, we report a longitudinal data set collected from 19 patients with subcortical stroke and 11 controls. Patients were imaged up to five times over 1 year. We found no evidence, using rs-fMRI, for longitudinal poststroke cortical connectivity changes despite substantial behavioral recovery. These results could be construed as questioning the value of resting-state imaging. Here, we argue instead that they are consistent with other emerging reasons to challenge the idea of motor-recovery-related cortical reorganization poststroke when conceived of as changes in connectivity between cortical areas. NEW & NOTEWORTHY We investigated longitudinal changes in functional connectivity after stroke. Despite substantial motor recovery, we found no differences in functional connectivity patterns between patients and controls, nor any changes over time. Assuming that rs-fMRI is an adequate method to capture connectivity changes between cortical regions after brain injury, these results provide reason to doubt that changes in cortico-cortical connectivity are the relevant mechanism for promoting motor recovery

Intermanual Differences in movement-related interhemispheric inhibition

Interhemispheric inhibition (IHI) between motor cortical areas is thought to play a critical role in motor control and could influence manual dexterity. The purpose of this study was to investigate IHI preceding movements of the dominant and nondominant hands of healthy volunteers. Movement-related IHI was studied by means of a double-pulse transcranial magnetic stimulation protocol in right-handed individuals in a simple reaction time paradigm. IHI targeting the motor cortex contralateral (IHI(c)) and ipsilateral (IHI(i)) to each moving finger was determined. IHI(c) was comparable after the go signal, a long time preceding movement onset, in both hands. Closer to movement onset, IHI(c) reversed into facilitation for the right dominant hand but remained inhibitory for left nondominant hand movements. IHI(i) displayed a nearly constant inhibition with a trough early in the premovement period in both hands. In conclusion, our results unveil a more important modulation of interhemispheric interactions during generation of dominant than nondominant hand movements. This modulation essentially consisted of a shift from a balanced IHI at rest to an IHI predominantly directed toward the ipsilateral primary motor cortex at movement onset. Such a mechanism might release muscles from inhibition in the contralateral primary motor cortex while preventing the occurrence of the mirror activity in ipsilateral primary motor cortex and could therefore contribute to intermanual differences in dexterity

Variable Neural Contributions to Explicit and Implicit Learning During Visuomotor Adaptation

We routinely make fine motor adjustments to maintain optimal motor performance. These adaptations have been attributed to both implicit, error-based mechanisms, and explicit, strategy-based mechanisms. However, little is known about the neural basis of implicit vs. explicit learning. Here, we aimed to use anodal transcranial direct current stimulation (tDCS) to probe the relationship between different brain regions and learning mechanisms during a visuomotor adaptation task in humans. We hypothesized that anodal tDCS over the cerebellum (CB) should increase implicit learning while anodal tDCS over the dorsolateral prefrontal cortex (dlPFC), a region associated with higher-level cognition, should facilitate explicit learning. Using a horizontal visuomotor adaptation task that measures explicit/implicit contributions to learning (Taylor et al., 2014), we found that dlPFC stimulation significantly improved performance compared to the other groups, and weakly increased explicit learning. However, CB stimulation had no effects on either target error or implicit learning. Previous work showed variable CB stimulation effects only on a vertical visuomotor adaptation task (Jalali et al., 2017), so in Experiment 2, we conducted the same study using a vertical context to see if we could find effects of CB stimulation. We found only weak effects of CB stimulation on target error and implicit learning, and now the dlPFC effect did not replicate. To resolve this discrepancy, in Experiment 3, we examined the effect of context (vertical vs. horizontal) on implicit and explicit contributions and found that individuals performed significantly worse and used greater implicit learning in the vertical screen condition compared to the horizontal screen condition. Across all experiments, however, there was high inter-individual variability, with strong influences of a few individuals, suggesting that these effects are not consistent across individuals. Overall, this work provides preliminary support for the idea that different neural regions can be engaged to improve visuomotor adaptation, but shows that each region's effects are highly context-dependent and not clearly dissociable from one another. This holds implications especially in neurorehabilitation, where an intact neural region could be engaged to potentially compensate if another region is impaired. Future work should examine factors influencing interindividual variability during these processes