These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

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The extent of synchronization within and between the nuclei of the basal ganglia is unknown in Parkinson's disease. The question is an important one because synchronization will increase postsynaptic efficacy at subsequent projection targets. We simultaneously recorded local potentials (LPs) from the globus pallidus interna (GPi) and subthalamic nucleus (STN) in four awake patients after neurosurgery for Parkinson's disease. Nuclei from both sides were recorded in two patients so that a total of six ipsilateral GPi-STN LP recordings were made. Without medication, the power within and the coherence between the GPi and STN was dominated by activity with a frequency Ͻ30 Hz. Treatment with the dopamine precursor levodopa reduced the low-frequency activity and resulted in a new peak at ϳ70 Hz. This was evident in the power spectrum from STN and GPi and in the coherence between these nuclei. The phase relationship between the nuclei varied in a complex manner according to frequency band and the presence of exogenous dopaminergic stimulation. Synchronization of activity does occur between pallidum and STN, and its pattern is critically dependent on the level of dopaminergic activity.Key words: globus pallidus interna; subthalamic nucleus; coherence; synchronization; Parkinson's disease; dopamine Studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated primates and in patients with Parkinson's disease have found an increase in firing rate and a tendency toward bursting in the neurons of the globus pallidus interna (GPi) and subthalamic nucleus (STN) (Filion and Tremblay, 1991;Bergman et al., 1994;Sterio et al., 1994;Hutchison et al., 1997aHutchison et al., , 1998Merello et al., 1999). These changes are likely to influence the projection targets of the basal ganglia in the thalamus and brainstem, although not as much as if the postsynaptic efficacy of neuronal activity was increased through the synchronization of discharges emanating from these nuclei. There is some evidence for the synchronization of neuronal discharges within the GPi of MPTP-treated primates (Nini et al., 1995), but, to date, there is no evidence for significant synchronization in patients with Parkinson's disease.Here we look for synchronization within and between the human GPi and ipsilateral STN in the presence and relative absence of dopaminergic stimulation, by recording from the basal ganglia in patients undergoing functional neurosurgery for severe Parkinson's disease. Patients were recorded after withdrawal and reinstitution of treatment with the dopamine precursor levodopa, which elevates levels of dopamine and its metabolites in the parkinsonian brain, without significant change in noradrenaline or serotonin (Scatton et al., 1983). To avoid surgery-related time constraints, we recorded local potentials (LPs) postoperatively from the different contacts of macroelectrodes rather than the action potentials of individual neurons using intraoperative microelectrodes. The use of bipolar contacts increased the likelihood that only loca...

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1. EMG responses evoked in hand muscles by transcranial stimulation over the motor cortex were conditioned by a single motor threshold electrical stimulus to the median nerve at the wrist in a total of ten healthy subjects and in five patients who had electrodes implanted chronically into the cervical epidural space. 2. The median nerve stimulus suppressed responses evoked by transcranial magnetic stimulation (TMS) in relaxed or active muscle. The minimum interval between the stimuli at which this occurred was 19 ms. A similar effect was seen if electrical stimulation was applied to the digital nerves of the first two fingers. 3. Median or digital nerve stimulation could suppress the responses evoked in active muscle by transcranial electrical stimulation over the motor cortex, but the effect was much less than with magnetic stimulation. 4. During contraction without TMS, both types of conditioning stimuli evoked a cutaneomuscular reflex that began with a short period of inhibition. This started about 5 ms after the inhibition of responses evoked by TMS. 5. Recordings in the patients showed that median nerve stimulation reduced the size and number of descending corticospinal volleys evoked by magnetic stimulation. 6. We conclude that mixed or cutaneous input from the hand can suppress the excitability of the motor cortex at short latency. This suppression may contribute to the initial inhibition of the cutaneomuscular reflex. Reduced spinal excitability in this period could account for the mild inhibition of responses to electrical brain stimulation.

Noninvasive brain stimulation (NIBS) techniques can be used to monitor and modulate the excitability of intracortical neuronal circuits. Long periods of cortical stimulation can produce lasting effects on brain function, paving the way for therapeutic applications of NIBS in chronic neurological disease. The potential of NIBS in stroke rehabilitation has been of particular interest, because stroke is the main cause of permanent disability in industrial nations, and treatment outcomes often fail to meet the expectations of patients. Despite promising reports from many clinical trials on NIBS for stroke recovery, the number of studies reporting a null effect remains a concern. One possible explanation is that the interhemispheric competition model--which posits that suppressing the excitability of the hemisphere not affected by stroke will enhance recovery by reducing interhemispheric inhibition of the stroke hemisphere, and forms the rationale for many studies--is oversimplified or even incorrect. Here, we critically review the proposed mechanisms of synaptic and functional reorganization after stroke, and suggest a bimodal balance-recovery model that links interhemispheric balancing and functional recovery to the structural reserve spared by the lesion. The proposed model could enable NIBS to be tailored to the needs of individual patients.

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