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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.)

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.)