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Subtle clinical cerebellar alterations have been found in migraine. Moreover, abnormalities in visual and motor cortex excitability consistent with a lack of inhibitory efficiency have been described in migraine, and it is known that cerebellum exerts an inhibitory control on cerebral cortex. Here, we investigated if impairment of cerebellar activity on motor cortex, i.e. reduced inhibitory control, can be found in migraine. Ten migraineurs with aura and seven healthy controls underwent a transcranial magnetic stimulation (TMS) protocol to investigate the cerebellar inhibitory drive on motor cortex: a conditioning pulse on right cerebellar cortex was delivered 5, 7, 10, 15 ms before a test stimulus (TS) on contralateral motor cortex. The cerebellar conditioning stimulus inhibits the size of the motor-evoked potential (MEP) produced by the TS alone by approximately 30-50%. Amplitude of MEP to TS alone showed no significant difference between patients and controls. Cerebellar conditioning TMS showed a significant deficit of cerebellar inhibition in migraine patients as compared to controls at all interstimulus intervals (5-15 ms) tested. Cerebellar inhibition is reduced in migraineurs. This could account, at least in part, for the reduced inhibitory efficiency previously showed in cerebral cortex of these patients.

Objective To investigate electrophysiologically the reproducibility of oropharyngeal swallowing in patients with ALS. Methods We enrolled 26 ALS patients, both with and without clinical signs of dysphagia, and 30 age-matched controls. The reproducibility of the electrophysiological signals related to the oral phase (electromyographic activity of the submental/suprahyoid muscles) and the pharyngeal phase (laryngeal-pharyngeal mechanogram) of swallowing across repeated swallows was assessed. To do this we computed two similarity indexes (SI) by using previously described mathematical algorithms. Results The reproducibility of oropharyngeal swallowing was significantly reduced both in patients with and in those without clinical signs of dysphagia, with more marked alterations being detected in the dysphagic group. The SI of both phases of swallowing, oral and pharyngeal, correlated significantly with dysphagia severity and disease severity. Conclusions In ALS different pathophysiological mechanisms can alter the stereotyped motor behaviors underlying normal swallowing, thus reducing the reproducibility of the swallowing act. A decrease in swallowing reproducibility could be a preclinical sign of dysphagia and, beyond a certain threshold, a pathological hallmark of oropharyngeal dysphagia. Significance Electrophysiological assessment is a simple and useful tool for the early detection of swallowing abnormalities, and for the management of overt dysphagia in ALS.

Experimental evidence suggests impairment of inhibitory intracortical circuits in migraine, while not much is known about activity of facilitatory intracortical circuits. In the present work we evaluated the effects of high frequency-repetitive transcranial magnetic stimulation (hf-rTMS) on the activity of facilitatory circuits of motor cortex in 18 patients affected by migraine with aura and 18 healthy subjects. Trains of 10 stimuli were applied to the motor cortex at 5-Hz frequency with recording of the EMG traces from the contralateral abductor pollicis brevis muscle (APB). Two intensities of stimulation (110% and 130% of resting motor threshold) were used in order to explore whether motor cortex excitability was differently modulated. Twelve patients underwent hf-rTMS both before and during prophylactic treatment with levetiracetam. Results showed that rTMS delivered at 110% intensity of stimulation at rest had a facilitatory effect on MEP size in untreated patients, while left MEP unchanged in controls. Conversely, when rTMS was applied at 130%, we observed MEP potentiation in healthy subjects and paradoxical MEP inhibition in migraineurs. In treated patients, levetiracetam inhibited MEP size at both 110% and 130% intensity of stimulation. Our findings reveal an opposite response of migraine motor cortex to 5-Hz rTMS when it is delivered at different stimulation intensities, providing evidence of both hyper-responsivity and self-limiting hyperexcitability capacity, in line with studies supporting the concept that under conditions of cortical hyperexcitability inhibitory mechanisms of homeostatic plasticity could be activated.

Electrophysiological assessment provides valuable information on physiological and pathophysiological characteristics of human swallowing. Here, new electrophysiological measures for the evaluation of oropharyngeal swallowing were assessed: (1) the activation pattern of the submental/suprahyoid EMG activity (SHEMG); (2) the reproducibility of the oral and pharyngeal phases of swallowing, by calculating the similarity index (SI) of the SHEMG (SI-SHEMG) and of the laryngeal-pharyngeal mechanogram (SI-LPM) during repeated swallows; and (3) kinesiological measures related to the LPM. An electrophysiological-mechanical method for measuring the activation pattern of the SHEMG, the SI-SHEMG, and the SI-LPM, and maximal LPM velocity and acceleration during swallowing was applied in 65 healthy subjects divided into three age groups (18-39, 40-59, 60 years or over). All the measures were assessed during three trials of eight consecutive swallows of different liquid bolus volumes (3, 12, and 20 ml). A high overall reproducibility of oropharyngeal swallowing in healthy humans was recorded. However, while values of SI-SHEMG were similar in all the age groups, the SI-LPM was found to fall significantly in the older age group. Both the SI-SHEMG and the SI-LPM were found to fall with increasing bolus volumes. The activation pattern of the SHEMG and the LPM kinesiological measures were differently modified by bolus volume and age in the older subjects with respect to the others. We describe a new approach to the electrophysiological study of swallowing based on computed semi-automatic analyses. Our findings provide insight into some previously uninvestigated aspects of oropharyngeal swallowing physiology, considered in relation to bolus volume and age. The new electrophysiological measures here described could prove useful in the clinical setting, as it is likely that they could be differently affected in patients with different kinds of dysphagia.

Background Transcranial direct current stimulation (tDCS) is a non-invasive technique used for modulating cortical excitability in vivo in humans. Here we evaluated the effect of tDCS on behavioral and electrophysiological aspects of physiological sucking and swallowing. Methods Twelve healthy subjects underwent three tDCS sessions (anodal, cathodal and sham stimulation) on separate days in a double-blind randomized order. The active electrode was placed over the right swallowing motor cortex. Repeated sucking and swallowing acts were performed at baseline and at 15 and 60 min after each tDCS session and the mean liquid bolus volume ingested at each time point was measured. We also calculated average values of the following electrophysiological parameters: 1) area and 2) duration of the rectified EMG signal from the suprahyoid/submental muscles related to the sucking and swallowing phases; 3) EMG peak amplitude for the sucking and swallowing phases; 4) area and peak amplitude of the laryngeal-pharyngeal mechanogram; 5) oropharyngeal delay. Results The volume of the ingested bolus significantly increased (by an average of about 30% compared with the baseline value) both at 15 and at 60 min after the end of anodal tDCS. The electrophysiological evaluation after anodal tDCS showed a significant increase in area and duration of the sucking phase-related EMG signal. Conclusions Anodal tDCS leads to stronger sucking of a liquid bolus in healthy subjects, likely by increasing recruitment of cortical areas of the swallowing network. This finding might open up interesting perspectives for the treatment of patients suffering from dysphagia due to various pathological conditions.

The primary brain dysfunctions leading to the onset of a migraine attack remain largely unknown. Other important open questions concern the mechanisms of initiation, continuation, and termination of migraine pain, and the changes in brain function underlying migraine transformation. Brief trains of high-frequency repetitive transcranial magnetic stimulation (rTMS), when applied to the primary motor cortex at suprathreshold intensity (⩾120% of resting motor threshold [RMT]), elicit in healthy subjects a progressive, glutamate-dependent facilitation of the motor evoked potentials (MEP). Conversely, in conditions of increased cortical excitability, the rTMS trains induce inhibitory MEP responses likely mediated by cortical homeostatic mechanisms. We enrolled 66 migraine-without-aura patients, 48 migraine-with-aura patients, 14 patients affected by chronic migraine (CM), and 20 healthy controls. We assessed motor cortical response to 5-Hz rTMS trains of 10 stimuli given at 120% RMT. Patients with episodic migraine were studied in different phases of the migraine cycle: interictal, preictal, ictal, and postictal states. Results showed a facilitatory MEP response during the trains in patients evaluated in the preictal phase, whereas inhibitory responses were observed during and after a migraine attack, as well as in CM patients. In the interictal phase, different responses were observed, depending on attack frequency: facilitation in patients with low and inhibition in those with high attack recurrence. Our findings suggest that changes in cortical excitability and fluctuations in the threshold for inhibitory metaplasticity underlie the migraine attack recurrence, and could be involved in the process of migraine transformation.