Changes in cerebellar output abnormally modulate cortical myoclonus sensorimotor hyperexcitability

Abstract

Cortical myoclonus is produced by abnormal neuronal discharges within the sensorimotor cortex, as demonstrated by electrophysiology. Our hypothesis is that the loss of cerebellar inhibitory control over the motor cortex, via cerebello-thalamo-cortical connections, could induce the increased sensorimotor cortical excitability that eventually causes cortical myoclonus. To explore this hypothesis, in the present study we applied anodal transcranial direct current stimulation over the cerebellum of patients affected by cortical myoclonus and healthy controls and assessed its effect on sensorimotor cortex excitability. We expected that anodal cerebellar transcranial direct current stimulation would increase the inhibitory cerebellar drive to the motor cortex and therefore reduce the sensorimotor cortex hyperexcitability observed in cortical myoclonus. Ten patients affected by cortical myoclonus of various aetiology and 10 aged-matched healthy controls were included in the study. All participants underwent somatosensory evoked potentials, long-latency reflexes, and short-interval intracortical inhibition recording at baseline and immediately after 20 min session of cerebellar anodal transcranial direct current stimulation. In patients, myoclonus was recorded by the means of surface electromyography before and after the cerebellar stimulation. Anodal cerebellar transcranial direct current stimulation did not change the above variables in healthy controls, while it significantly increased the amplitude of somatosensory evoked potential cortical components, long-latency reflexes and decreased short-interval intracortical inhibition in patients; alongside, a trend towards worsening of the myoclonus after the cerebellar stimulation was observed. Interestingly, when dividing patients in those with and without giant somatosensory evoked potentials, the increment of the somatosensory evoked potential cortical components was observed mainly in those with giant potentials. Our data showed that anodal cerebellar transcranial direct current stimulation facilitates, and does not inhibit, sensorimotor cortex excitability in cortical myoclonus syndromes. This paradoxical response might be due to an abnormal homeostatic plasticity within the sensorimotor cortex, driven by dysfunctional cerebello-thalamo-cortical input to the motor cortex. We suggest that the cerebellum is implicated in the pathophysiology of cortical myoclonus and that these results could open the way to new forms of treatment or treatment targets.

Cerebellar Non-Invasive Brain Stimulation: A Frontier in Chronic Pain Therapy

“…TDCS involves the administration of a weak (1-2 mA) direct current, between two or more electrodes, usually for 15-25 min, causing alterations in the neuronal resting membrane potential, with polarity-specific effects: anodal stimulation generally enhances cortical excitability, while cathodal stimulation is thought to operate in an opposite way by depolarizing or hyperpolarizing the membrane potential [100]. These effects on membrane polarization are proposed to be paralleled by changes in spontaneous firing rates [101,102]. Cerebellar tDCS can modulate the membrane polarization of Purkinje and glial cells, as well as mossy and climbing fibres [103,104].…”