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The cerebellum is strongly implicated in learning new motor skills. Theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation, can be used to influence cerebellar activity. Our aim was to explore the potential of cerebellar TBS in modulating visuo-motor adaptation, a form of motor learning, in young healthy subjects. Cerebellar TBS was applied immediately before the learning phase of a visuo-motor adaptation task (VAT), in two different experiments. Firstly, we evaluated the behavioral effects of continuous (cTBS), intermittent (iTBS) or sham TBS on the learning, re-adaptation and de-adaptation phases of VAT. Subsequently, we investigated the changes induced by iTBS or sham TBS on motor cortical activity related to each phase of VAT, as measured by concomitant TMS/EEG recordings. We found that cerebellar TBS induced a robust bidirectional modulation of the VAT performance. More specifically, cerebellar iTBS accelerated visuo-motor adaptation, by speeding up error reduction in response to a novel perturbation. This gain of function was still maintained when the novel acquired motor plan was tested during a subsequent phase of re-adaptation. On the other hand, cerebellar cTBS induced the opposite effect, slowing the rate of error reduction in both learning and re-adaptation phases. Additionally, TMS/EEG recordings showed that cerebellar iTBS induced specific changes of cortical activity in the interconnected motor networks. The improved performance was accompanied by an increase of TMS-evoked cortical activity and a generalized desynchronization of TMS-evoked cortical oscillations. Taken together, our behavioral and neurophysiological findings provide the first-time multimodal evidence of the potential efficacy of cerebellar TBS in improving motor learning, by promoting successful cerebellar-cortical reorganization., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier Inc.)

Since early days after stroke, the brain undergoes a complex reorganization to allow compensatory mechanisms that promote functional recovery. However, these mechanisms are still poorly understood and there is urgent need to identify neurophysiological markers of functional recovery after stroke. Here we aimed to track longitudinally the time-course of cortical reorganization by measuring for the first time EEG cortical activity evoked by TMS pulses in patients with subcortical stroke. Thirteen patients in the sub-acute phase of ischemic subcortical stroke with motor symptoms completed the longitudinal study, being evaluated within 20 days and after 40, 60 and 180 days after stroke onset. For each time-point, EEG cortical activity evoked by single TMS pulses was assessed over the motor and parietal cortex of the affected and unaffected hemisphere. We evaluated global TMS-evoked activity and TMS-evoked oscillations in different frequency bands. These measurements were paralleled with clinical and behavioral assessment. We found that motor cortical activity measured by TMS-EEG varied across time in the affected hemisphere. An increase of TMS-evoked activity was evident at 40 days after stroke onset. Moreover, stroke patients showed a significant increase in TMS-evoked alpha oscillations, as highlighted performing analysis in the time-frequency domain. Notably, these changes indicated that crucial mechanisms of cortical reorganization occur in this short-time window. These changes coincided with the clinical improvement. TMS-evoked alpha oscillatory activity recorded at baseline was associated to better functional recovery at 40 and 60 days' follow-up evaluations, suggesting that the power of the alpha rhythm can be considered a good predictor of motor recovery. This study demonstrates that cortical activity increases dynamically in the early phases of recovery after stroke in the affected hemisphere. These findings point to TMS-evoked alpha oscillatory activity as a potential neurophysiological markers of stroke recovery and could be helpful to determine the temporal window in which neuromodulation should be potentially able to drive neuroplasticity in an effective functional direction., (Copyright © 2018. Published by Elsevier Inc.)

Context: Osteopathic manipulative therapy (OMTh; manipulative care provided by foreign-trained osteopaths) is effective in managing pain caused by a variety of clinical conditions. Nevertheless, the physiologic mechanisms at the basis of the clinical improvement are poorly understood., Objective: To investigate the effects of OMTh, muscle stretching, and soft touch interventions on motor cortical excitability through a rapid-rate paired associative stimulation (PAS) protocol., Methods: In this crossover study, participants underwent OMTh, muscle stretching, and soft touch interventions. A rapid-rate PAS transcranial magnetic stimulation protocol was performed immediately after each intervention session, which consisted of 600 pairs of stimuli continuously delivered to the left primary motor cortex and to the right median nerve at a rate of 5 Hz for 2 minutes. The interstimulus intervals between the peripheral stimulus and the transcranial magnetic stimulation was set at 25 milliseconds. Before and after rapid-rate PAS (immediately after and 15 minutes after), changes in the amplitude of the motor evoked potentials were measured in the right abductor pollicis brevis and the right first dorsal interosseous., Results: Of the potential 15 participants initially recruited, 12 fit the inclusion criteria. Two of the 12 participants were excluded from the final analysis because of excessive artifact movements. Rapid-rate PAS induced a more pronounced, longer-lasting increase in cortical excitability in the abductor pollicis brevis muscle in patients 15 minutes after the OMTh intervention than after the muscle stretching or sham interventions (P=.016)., Conclusion: Results of the current study provide support for the effects of OMTh on cortical plasticity.

We injected wheat germ agglutinin conjugated to horseradish peroxidase into different segments of the spinal cord in order to examine the topographic organization of corticospinal projections from the medial wall of the hemisphere. We observed that substantial projections to the spinal cord originate not only from the supplementary motor area (SMA) in area 6, but also from 2 regions within the cingulate sulcus. The distribution of labeled neurons following tracer injections into different spinal cord segments indicates that corticospinal projections from the SMA and from the 2 cingulate regions are somatotopically organized. These findings together with other recent anatomical observations suggest that the corticospinal projections from the medial wall of the hemisphere provide the basal ganglia and limbic system with a somatotopically organized access to spinal cord mechanisms.

We investigated the patterns of corticospinal projection to different segments of the cervical spinal cord using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. We confirmed prior suggestions that the arcuate premotor area (APA) has a significant projection to the spinal cord. In addition, we observed that the corticospinal projection from the APA terminates in upper, but not lower segments of the cervical spinal cord. Furthermore, the region of the APA which projects to the cervical cord also projects to the arm area of the primary motor cortex on the crest of the precentral gyrus. Thus, we conclude that the APA projection to upper cervical segments is involved in the cortical control of arm movements.