| Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes.

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The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases.Here, the various invasive and non-invasive approaches, such as hypothalamic deep brain stimulation, occipital nerve stimulation, stimulation of sphenopalatine ganglion, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation are extensively published although proper RCT-based evidence is limited. The European Headache Federation herewith provides a consensus statement on the clinical use of neuromodulation in headache, based on theoretical background, clinical data, and side effect of each method. This international consensus further gives recommendations for future studies on these new approaches.In spite of a growing field of stimulation devices in headaches treatment, further controlled studies to validate, strengthen and disseminate the use of neurostimulation are clearly warranted. Consequently, until these data are available any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies with an acceptable side effect profile.

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Evidence by functional imaging studies suggests the role of left DLPFC in the inhibitory control of nociceptive transmission system. Pain exerts an inhibitory modulation on motor cortex, reducing MEP amplitude, while the effect of pain on motor intracortical excitability has not been studied so far. In the present study, we explored in healthy subjects the effect of capsaicin-induced pain and the modulatory influences of left DLPFC stimulation on motor corticospinal and intracortical excitability. Capsaicin was applied on the dorsal surface of the right hand, and measures of motor corticospinal excitability (test-MEP) and short intracortical inhibition (SICI) and facilitation (ICF) were obtained by paired-pulse TMS on left motor cortex. Evaluations were made before and at different times after capsaicin application in two separate sessions: without and with high-frequency rTMS of left DLPF cortex, delivered 10 min. after capsaicin application. We performed also two control experiments to explore: 1: the effects of Left DLPFC rTMS on capsaicin-induced pain; 2: the modulatory influence of left DLPFC rTMS on motor cortex without capsaicin application. Capsaicin-induced pain significantly reduced test MEP amplitude and decreased SICI leaving ICF unchanged. Left DLPFC rTMS, together with the analgesic effect, was able to revert the effects of capsaicin-induced pain on motor cortex restoring normal MEP and SICI levels. These data support the notion that that tonic pain exerts modulatory influence on motor intracortical excitability; the activation of left DLPFC by hf rTMS could have analgesic effects, reverting also the motor cortex excitability changes induced by pain stimulation.

Recent studies showed hyperexcitability of the occipital cortex in subjects affected by migraine with aura. It has been shown that 1 Hz repetitive transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in normal subjects. The aim of the study was to investigate the effects of low frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients with migraine with aura and 15 healthy controls were examined. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the PT (the lowest magnetic stimulation intensity at which subjects just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT intensity for 15 min. The difference in the proportion of subjects reporting phosphenes in migrainer and control groups was significant (migrainers: 100% vs controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a significantly increased visual cortex excitability expressed as a decrease in PT in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train normal subjects showed increased PT values, which suggests a decreased visual cortex excitability. Our findings confirm that the visual cortex is hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which are unable to be upregulated by low frequency rTMS.

To verify the role of interhemispheric influences on manifestations of neglect, the authors investigated the effects of a transient repetitive transcranial magnetic stimulation (rTMS)-induced disruption of the unaffected hemisphere on contralesional visuospatial neglect in two left- and five right-brain-damaged patients. Parietal rTMS of the unaffected hemisphere during the execution of a computerized task of bisected line's length judgment transiently decreased the magnitude of neglect as expressed in the number of errors.

Background and objective Progression of Parkinson's disease (PD) is frequently characterized by the occurrence of freezing of gait (FOG) representing a disabling motor complication. We aim to investigate safety and efficacy of transcranial direct current stimulation of the primary motor cortex of PD patients with FOG. Methods In this cross‐over, double‐blind, sham‐controlled study, 10 PD patients with FOG persisting in “on” state underwent anodal and sham direct current stimulation for 5 consecutive days. Clinical assessment over a 1‐month period was performed. Results A significant improvement of gait, as assessed by the Stand Walk Sit test, with reduction in number and duration of FOG episodes, along with a significant reduction in the Unified Parkinson's Disease Rating Scale score, were observed after anodal stimulation. Beneficial effects were more evident after the entire 5‐day stimulation session, and persisted until the end of the observation period. Conclusions Anodal transcranial direct current stimulation of the motor cortex is safe and has therapeutic potential in PD patients with FOG. © 2014 International Parkinson and Movement Disorder Society