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Background: We aimed at evaluating the amplitude changes of the motor evoked potentials (MEPs) induced by of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) in10 patients with primary insomnia (PI) and in 10 age-matched healthy controls., Methods: Median peak-to-peak MEP amplitudes were assessed in all subjects at three times: at baseline (T 0 ), after the first train of a single rTMS session (T 1 ), and after the whole rTMS procedure (T 2 ). This consists of 20 trains of 1 Hz stimulation with 50 stimuli per train and an intertrain interval of 30 s., Results: Resting motor threshold (RMT) and MEPs amplitude did not differ between the two groups at T 0 . A reduction of MEP size was observed at both T 1 and T 2 in all subjects, but this was significantly less pronounced in patients than in control subjects., Conclusions: The lack of MEP inhibition reflects an altered response to LF rTMS in patients with PI. These rTMS findings are indicative of an altered cortical plasticity in inhibitory circuits within M1 in PI. Subjects with PI exhibited an impairment of the LTD-like mechanisms induced by inhibitory rTMS, thus providing further support to the involvement of GABA neurotransmission in the pathophysiology of PI., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this review, we aimed at identifying the studies that have employed repetitive transcranial magnetic stimulation (rTMS) in patients with sleep disorders. Low-frequency (LF) rTMS stimulating the right dorsolateral prefrontal cortex (DLPFC) or the posterior parietal cortex (PPC) was found to be effective to reduce cortical hyperexcitability and improve the sleep quality in subjects with chronic primary insomnia (PI). Both high-frequency (HF) and LF rTMS applied over the primary motor cortex or the supplementary motor cortex seem to have transient beneficial effects in patients with restless legs syndrome (RLS). Stimulation of upper airway muscles during sleep by isolated TMS and by rTMS twitch can improve airflow dynamics in obstructive sleep apnea syndrome (OSAS) patients without arousal. A single case report study indicates that HF rTMS over the left DLPFC might represent an alternative choice for symptom control in narcoleptic patients with cataplexy, and a pilot study also raises the possibility of therapeutic benefits from rTMS in patients with sleep bruxism. rTMS may also exert intrinsic effects on hypersomnia in depressed adolescents. In conclusion, rTMS may contribute to the development of new non-pharmacological therapeutic options for several sleep disorders. rTMS might be useful as therapeutical tool in particular in patients with PI, RLS, OSAS and narcolepsy, while its effect in other sleep disorders (ie, parasomnias) has not yet been explored. rTMS integrated with clinical, sleep-related, and neuroimaging data may represent an effective tool in modulating cortical excitability and inducing short-term synaptic plasticity. Further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up warranted to verify the initial findings, and to expand clinical and research interest towards neuromodulation in the different sleep disorders., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Transcranial magnetic stimulation (TMS) may offer a reliable means to characterize significant pathophysiologic and neurochemical aspects of restless legs syndrome (RLS). Namely, TMS has revealed specific patterns of changes in cortical excitability and plasticity, in particular dysfunctional inhibitory mechanisms and sensorimotor integration, which are thought to be part of the pathophysiological mechanisms of RLS rather than reflect a non-specific consequence of sleep architecture alteration. If delivered repetitively, TMS is able to transiently modulate the neural activity of the stimulated and connected areas. Some studies have begun to therapeutically use repetitive TMS (rTMS) to improve sensory and motor disturbances in RLS. High-frequency rTMS applied over the primary motor cortex or the supplementary motor cortex, as well as low-frequency rTMS over the primary somatosensory cortex, seem to have transient beneficial effects. However, further studies with larger patient samples, repeated sessions, an optimized rTMS setup, and clinical follow-up are needed in order to corroborate preliminary results. Thus, we performed a systematic search of all the studies that have used TMS and rTMS techniques in patients with RLS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We provide here the first systematic review on the studies dealing with repetitive transcranial magnetic stimulation (rTMS) for traumatic brain injury (TBI) in animals and humans. Several experimental studies in animal models have explored with promising results the use of rTMS to enhance neuroprotection and recovery after TBI. However, there are surprisingly few studies that have obtained substantial evidence regarding effects of rTMS in humans with TBI, many of them are case reports investigating the heterogeneous conditions linked to TBI. The most studies have investigated the effects of rTMS in subjects with post-traumatic depression and variable effects have been observed. rTMS has been proposed as an experimental approach for the treatment of disorders of consciousness (DOC), but in subjects with TBI therapeutic effects on DOC have also been variously documented. Beneficial effects have been reported in subjects with cognitive/emotional disturbances and auditory dysfunction (tinnitus and hallucinations), although the results are somewhat conflicting. rTMS applied over the left prefrontal cortex may relieve, at least transiently, post-traumatic headache. Isolated rTMS studies have been performed in TBI patients with motor impairment, chronic dizziness or pain. Especially whether provided in combination, rTMS and neurorehabilitation may be synergistic in the potential to translate experimental findings in the clinical practice. In order to reach definitive conclusions, well-designed randomized controlled studies with larger patient samples, improved design and optimized rTMS setup, are warranted to verify and corroborate the initial promising findings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Several studies have applied transcranial magnetic stimulation (TMS) in the attempt to further explore the pathophysiological mechanisms of phantom-limb pain (PLP) and non-painful phantom sensations (PS). We performed a systematic review of available evidence of this emerging technology in this indication. We identified studies which report a reduced intracortical inhibition and increased intracortical facilitation in the hemisphere contralateral to the PLP. TMS mapping revealed a significant lateralization of the center of gravity and an enlargement of the excitable area on the hemisphere contralateral to the amputation. N-Methyl-d-Aspartate-mediated mechanisms influence the changes of intracortical inhibition and facilitation occurring after limb amputation; however, these cortical excitability changes and PLP are independent of each other. TMS can also influence brain function if applied repetitively. A few studies have begun to therapeutically use repetitive TMS (rTMS) to relief PLP and non-painful PS. rTMS of the contralateral parietal cortex lead to a transient reduction in pain intensity. High frequency rTMS applied over the contralateral motor cortex (M1) or low frequency rTMS over the unaffected hemisphere might also induce significant clinical improvement in PLP. On the other hand, serum beta-endorphin increased significantly after real stimulation over contralateral M1. This systematic review illustrates that TMS technique is an emerging tool to gain insights to pathophysiological aspects of pain and non-painful phantom phenomena. Moreover, TMS could support appropriate patient selection for different therapies and may also have therapeutic utility in subjects with PLP or PS, though the evidence is still very preliminary and well-designed studies in larger cohort of patients are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Transcranial magnetic stimulation (TMS) may represent a valuable tool for investigating important neurophysiological and pathophysiological aspects of myoclonus. Moreover, repetitive TMS (rTMS) can influence neural activity. In this review we performed a systematic search of all studies using TMS in order to explore cortical excitability/plasticity and rTMS for the treatment of myoclonus due to different aetiologies. We identified and reviewed 40 articles matching the inclusion criteria; 415 patients were included in these studies. The reviewed TMS studies have detected abnormalities in motor cortex excitability and sensorimotor plasticity. The most consistent finding is a decrease in intracortical inhibition. Short-interval intracortical inhibition (SICI) is reduced in myoclonic epilepsies. Unlike the juvenile and the benign myoclonus epilepsy, long-interval intracortical inhibition, interhemispheric inhibition and sensorimotor integration were altered in patients with progressive myoclonic epilepsies. In patients with myoclonus-dystonia the results are partly conflicting. Cortical membrane excitability was impaired while parameters assessing cortical synaptic activity were normal in DYT11 gene carriers. In other studies normal SICI suggests that the GABAergic cortical circuits are largely intact and that the mechanisms of myoclonus-dystonia are different from those for cortical myoclonus and other dystonic disorders. In conclusion, different TMS study protocols have provided new insights into sensorimotor plasticity and cortical excitability of the different forms of myoclonus, and have shed some light on the pathophysiology of this movement disorder. Well-defined motor cortical excitability patterns can be identified in the different disorders characterized by myoclonus, even if preliminary findings should be confirmed in future studies in larger cohorts of patients. Repetitive TMS might have therapeutic potential at least in some patients with myoclonus, similar to that reported in other neurological and psychiatric disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Neuroimaging studies suggest that spinal cord injury (SCI) may lead to significant anatomical alterations in the human sensorimotor system. In particular, voxel-based morphometry (VBM) of cortical volume has revealed a significant gray and white matter atrophy bilaterally in the primary sensory cortex (S1). By contrast, some structural studies failed to detect changes in gray matter volume (GMV) in the primary motor cortex (M1) following SCI, whereas others have reported a substantial decrease of GMV also in M1. In addition to direct degeneration of the sensorimotor cortex, SCI can also lead to atrophy of the non-sensorimotor cortex, such as anterior cingulate cortex, insular cortex, middle frontal gyrus and supplementary motor area. These findings suggest that SCI can cause remote atrophy of brain gray matter in the salient network. Furthermore, pain-related remodelling may occur in SCI. In fact, structural changes in SCI are also related to the presence and degree of below-level pain. We performed a systematic review of the neuroimaging studies showing morphometric cortical changes and subsequent functional reorganization in humans with SCI. Literature search was conducted using PubMed and Embase. We identified 12 articles matching the inclusion criteria and 195 patients were included in these studies. The wide range of disease duration, rehabilitation training, drug intervention, and different research methodology, especially the identification of region of interest and the statistical approach to correct for multiple comparisons, may have contributed to some inconsistencies between the reviewed studies. Nevertheless, neuroimaging biomarkers can assess the extent of neural damage, elucidate the mechanisms of neural repair, and predict clinical outcome. A better understanding of the structural and functional changes that occur at cortical level following SCI may be useful in tracking potential treatment induced changes and identifying potential therapeutic targets, thus developing evidence-based rehabilitation therapies., (Copyright © 2017. Published by Elsevier Inc.)

Background/objective: Odor identification and discrimination are reduced in subjects with obstructive sleep apnea syndrome (OSAS), but the pathophysiology of the olfactory dysfunction in OSAS is still poorly understood. Experimental evidence suggests that olfactory impairment could be related to central cholinergic dysfunction. Short latency afferent inhibition (SAI) is a paired-pulse transcranial magnetic stimulation (TMS) protocol that gives the opportunity to test an inhibitory cholinergic circuit in the human cerebral motor cortex. The objective of the study was to assess the cholinergic function, as measured by SAI, in OSAS patients with olfactory impairment., Methods: We applied SAI technique in 20 patients with OSAS and in 20 healthy control subjects; SAI values were correlated with the Sniffin' Sticks olfactory test results., Results: SAI was reduced in OSAS patients when compared with control subjects. We also found a strong negative correlation between olfactory parameters and SAI., Conclusions: These findings suggest that cholinergic dysfunction is a robust determinant of hyposmia also in OSAS patients. Reduced SAI values and presence of olfactory impairment might indicate an increased risk of cognitive decline in patients with OSAS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Hemispherectomy (HS) is an effective surgical procedure aimed at managing otherwise intractable epilepsy in cases of diffuse unihemispheric pathologies. Neurological recovery in subjects treated with HS is not limited to seizure reduction, rather, sensory-motor and behavioral improvement is often observed. This outcome highlights the considerable capability of the brain to react to such an extensive lesion, by functionally reorganizing and rewiring the cerebral cortex, especially early in life. In this narrative review, we summarize the animal studies as well as the human neurophysiological and neuroimaging studies dealing with the reorganizational processes that occur after HS. These topics are of particular interest in understanding mechanisms of functional recovery after brain injury. HS offers the chance to investigate contralesional hemisphere activity in controlling ipsilateral limb movements, and the role of transcallosal interactions, before and after the surgical procedure. These post-injury neuroplastic phenomena actually differ from those observed after less extensive brain damage. Therefore, they illustrate how different lesions could lead the contralesional hemisphere to play the "good" or "bad" role in functional recovery. These issues may have clinical implications and could inform rehabilitation strategies aiming to improve functional recovery following unilateral hemispheric lesions. Future studies, involving large cohorts of hemispherectomized patients, will be necessary in order to obtain a greater understanding of how cerebral reorganization can contribute to residual sensorimotor, visual and auditory functions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Most anti-parkinsonian drugs produce a dopamine-like effect on single dopaminergic neurons. Using electrophysiological recordings, this effect is observed as an inhibition of the spontaneous firing activity. The firing activity of dopaminergic cells throughout dopamine-mediated mechanisms is inhibited not only by dopamine direct agonists but also by substances that increase the release or synthesis, or block the uptake or reduce degradation of dopamine in the brain. Here we propose the electrophysiological approach on dopaminergic neurons in in vitro slice preparation as a preliminary tool for selecting new potential anti-parkinsonian agents, before they are tested in more complex animal models.