Background. Our goal was to perform a systematic review on the use of repetitive transcranial magnetic stimulation (rTMS) in the treatment of status epilepticus (SE) and refractory status epilepticus (RSE). Methods. MEDLINE, BIOSIS, EMBASE, Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to August 2015), and gray literature were searched. The strength of evidence was adjudicated using Oxford and GRADE methodology. Results. We identified 11 original articles. Twenty-one patients were described, with 13 adult and 8 pediatric. All studies were retrospective. Seizure reduction/control with rTMS occurred in 15 of the 21 patients (71.4%), with 5 (23.8%) and 10 (47.6%) displaying partial and complete responses, respectively. Seizures recurred after rTMS in 73.3% of the patients who had initially responded. All studies were an Oxford level 4, GRADE D level of evidence. Conclusions. Oxford level 4, GRADE D evidence exists to suggest a potential impact on seizure control with the use of rTMS for FSE and FRSE, though durability of the therapy is short-lived. Routine use of rTMS in this context cannot be recommended at this time. Further prospective study of this intervention is warranted.

As space agencies aim to reach and build installations on Mars, the crews will face longer exposure to extreme environments that may compromise their health and performance. Transcranial magnetic stimulation (TMS) is a painless non-invasive brain stimulation technique that could support space exploration in multiple ways. However, changes in brain morphology previously observed after long-term space missions may impact the efficacy of this intervention. We investigated how to optimize TMS for spaceflight-associated brain changes. Magnetic resonance imaging T1-weighted scans were collected from 15 Roscosmos cosmonauts and 14 non-flyer participants before, after 6 months on the International Space Station, and at a 7-month follow-up. Using biophysical modeling, we show that TMS generates different modeled responses in specific brain regions after spaceflight in cosmonauts compared to the control group. Differences are related to spaceflight-induced structural brain changes, such as those impacting cerebrospinal fluid volume and distribution. We suggest solutions to individualize TMS to enhance its efficacy and precision for potential applications in long-duration space missions.

Orienting covert exogenous (involuntary) attention to a target location improves performance in many visual tasks [1, 2]. It is unknown whether early visual cortical areas are necessary for this improvement. To establish a causal link between these areas and attentional modulations, we used transcranial magnetic stimulation (TMS) to briefly alter cortical excitability and determine whether early visual areas mediate the effect of exogenous attention on performance. Observers performed an orientation discrimination task. After a peripheral valid, neutral, or invalid cue, two cortically magnified gratings were presented, one in the stimulated region and the other in the symmetric region in the opposite hemifield. Observers received two successive TMS pulses around their occipital pole while the stimuli were presented. Shortly after, a response cue indicated the grating whose orientation observers had to discriminate. The response cue either matched-target stimulated-or did not match-distractor stimulated-the stimulated side. Grating contrast was varied to measure contrast response functions (CRF) for all combinations of attention and TMS conditions. When the distractor was stimulated, exogenous attention yielded response gain-performance benefits in the valid-cue condition and costs in the invalid-cue condition compared with the neutral condition at the high contrast levels. Crucially, when the target was stimulated, this response gain was eliminated. Therefore, TMS extinguished the effect of exogenous attention. These results establish a causal link between early visual areas and the modulatory effect of exogenous attention on performance.

One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca(2+) activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca(2+) activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.

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.

The quantification of stimulation intensity in transcranial magnetic stimulation (TMS) as a function of depth is of interest in order to adjust stimulator output when non-motor regions are stimulated. Currently, a linear increase of stimulator output to correct for depth has been suggested. This is contrary to the physical properties of the electric field that is induced by the stimulation coil as measured in vitro. For two stimulation coils, we determined the characteristics of their field in air. We then measured motor thresholds for the abductor hallucis muscle of 10 healthy subjects. Coil position, distance from the scalp, and orientation were controlled with a head tracking robotic system that corrected for head movements. In both coils an approximately exponential increase, rather than a linear increase, of the threshold with the scalp-coil distance was measured. The slope of the increase was slightly smaller than expected from the field characteristic, but overall in good agreement. With respect to the depth of the TMS target, different results were obtained from the threshold ratios of the coils and from the slopes of the threshold increase with distance. For the adjustment of stimulator output to scalp-to-cortex distances exponential functions with parameters motivated by physical properties of the coils should be used. Estimation of the target depth from the thresholds, with different coils, is not reliable. Our results resolve a conflict between physiological data and physical properties of TMS coils. They provide a more reliable base for depth dependent corrections for TMS stimulator output.

Some of trauma-exposed individuals develop posttraumatic stress disorder (PTSD), an incapacitating psychiatric disorder that is characterized by intrusion, avoidance, negative changes in mood and cognition, and hyperarousal. A number of other trauma-related conditions are very frequently found in individuals with PTSD. Traumatic brain injury (TBI) is one of the most frequently observed trauma-related conditions that trauma-exposed individuals with PTSD may experience. TBI refers to transient or permanent brain dysfunction that results in a wide range of neurological, cognitive, and psychiatric symptoms. These trauma-related conditions significantly affect one's quality of life, leading to substantial disability and socioeconomic burden. As the prevalence of PTSD with comorbid TBI is increasing in the general population along with the rates of crimes and accidents, effective prevention and intervention strategies are necessitated. However, a definitive treatment for PTSD with comorbid TBI is still lacking, resulting in high rates of treatment resistance and chronicity. It is essential to investigate the neurobiological mechanisms and potential therapeutics of PTSD with comorbid TBI. Yet, a few repetitive transcranial magnetic stimulation (rTMS) studies have recently investigated therapeutic efficacy in treatment-resistant patients with PTSD and/or TBI. Thus, this article reviews rTMS studies in trauma-related conditions, mainly focusing on PTSD and PTSD with TBI as one of the comorbidities. The review focuses on the applications of rTMS in reducing PTSD symptoms with and without comorbidities based on differential parameters and effects of rTMS as well as concomitant clinical conditions. The section on PTSD with comorbidities focuses on TBI with neurological, cognitive, and psychiatric symptoms. Although there were some inconsistencies in the clinical outcomes and optimized parameters of rTMS applied in PTSD and TBI, low frequency stimulation over the hyperactive frontal regions and/or high frequency stimulation over the hypoactive frontal regions generally improved the clinical symptoms of PTSD and TBI. Lastly, the limitations of the rTMS studies in PTSD and TBI as well as potential directions for future research are discussed.

Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer.

Transcranial magnetic stimulation (TMS) is increasingly being used to demonstrate the causal links between brain and behavior in humans. Further, extensive clinical trials are being conducted to investigate the therapeutic role of TMS in disorders such as depression. Because TMS causes strong peripheral effects such as auditory clicks and muscle twitches, experimental artifacts such as subject bias and placebo effect are clear concerns. Several sham TMS methods have been developed, but none of the techniques allows one to intermix real and sham TMS on a trial-by-trial basis in a double-blind manner. We have developed an attachment that allows fast, automated switching between Standard TMS and two types of control TMS (Sham and Reverse) without movement of the coil or reconfiguration of the setup. We validate the setup by performing mathematical modeling, search-coil and physiological measurements. To see if the stimulus conditions can be blinded, we conduct perceptual discrimination and sensory perception studies. We verify that the physical properties of the stimulus are appropriate, and that successive stimuli do not contaminate each other. We find that the threshold for motor activation is significantly higher for Reversed than for Standard stimulation, and that Sham stimulation entirely fails to activate muscle potentials. Subjects and experimenters perform poorly at discriminating between Sham and Standard TMS with a figure-of-eight coil, and between Reverse and Standard TMS with a circular coil. Our results raise the possibility of utilizing this technique for a wide range of applications.

Transcranial magnetic stimulation (TMS) is widely applied on humans for research and clinical purposes. TMS studies on small animals, e.g., rodents, can provide valuable knowledge of the underlying neurophysiological mechanisms. Administering TMS on small animals is, however, prone to technical difficulties, mainly due to their small head size. In this study, we aimed to develop an energy-efficient coil and a compatible experimental set-up for administering TMS on rodents. We applied a convex optimization process to develop a minimum-energy coil for TMS on rats. As the coil windings of the optimized coil extend to a wide region, we designed and manufactured a holder on which the rat lies upside down, with its head supported by the coil. We used the set-up to record TMS-electromyography, with electromyography recorded from limb muscles with intramuscular electrodes. The upside-down placement of the rat allowed the operator to easily navigate the TMS without the coil blocking their field of view. With this paradigm, we obtained consistent motor evoked potentials from all tested animals.

Many patients with bipolar disorder (BD) fail to experience benefit following traditional pharmacotherapy, necessitating alternative treatment options that will enable such patients to achieve remission. Transcranial magnetic stimulation (TMS) is a relatively new, noninvasive neuromodulation technique that involves the application of magnetic pulses on hyperactive or hypoactive cortical brain areas. We evaluated the existing literature on TMS as a treatment for BD across varied mood states.

Transcranial Direct Current Stimulation (tDCS) and Transcranial Magnetic Stimulation (TMS) have been described as promising alternatives to treat different pain syndromes. This study evaluated the effects of TMS and tDCS in the treatment of chronic orofacial pain, through a systematic review.

Converging evidence suggests that transcranial alternating current stimulation (tACS) may entrain endogenous neural oscillations to match the frequency and phase of the exogenously applied current and this entrainment may outlast the stimulation (although only for a few oscillatory cycles following the cessation of stimulation). However, observing entrainment in the electroencephalograph (EEG) during stimulation is extremely difficult due to the presence of complex tACS artifacts. The present study assessed entrainment to slow oscillatory (SO) tACS by measuring motor cortical excitability across different oscillatory phases during (i.e., online) and outlasting (i.e., offline) stimulation. 30 healthy participants received 60 trials of intermittent SO tACS (0.75 Hz; 16 s on/off interleaved) at an intensity of 2 mA peak-to-peak. Motor cortical excitability was assessed using transcranial magnetic stimulation (TMS) of the hand region of the primary motor cortex (M1HAND) to induce motor evoked potentials (MEPs) in the contralateral thumb. MEPs were acquired at four time-points within each trial - early online, late online, early offline, and late offline - as well as at the start and end of the overall stimulation period (to probe longer-lasting aftereffects of tACS). A significant increase in MEP amplitude was observed from pre- to post-tACS (paired-sample t-test; t29 = 2.64, P = 0.013, d = 0.48) and from the first to the last tACS block (t29 = -2.93, P = 0.02, d = 0.54). However, no phase-dependent modulation of excitability was observed. Therefore, although SO tACS had a facilitatory effect on motor cortical excitability that outlasted stimulation, there was no evidence supporting entrainment of endogenous oscillations as the underlying mechanism.

Prefrontal and temporo-parietal repetitive transcranial magnetic stimulation (rTMS) in patients suffering from chronic tinnitus have shown significant but only moderate effectiveness with high interindividual variability in treatment response. This open-label pilot study was designed to examine the general feasibility of an individualized fronto-temporal rTMS protocol and to explore what criteria are needed for a more detailed evaluation in randomized clinical studies.

Transcranial magnetic stimulation (TMS) is among a growing family of noninvasive brain stimulation techniques being developed to treat multiple neurocognitive disorders, including Alzheimer's disease (AD). Although small clinical trials in AD have reported positive effects on cognitive outcome measures, significant knowledge gaps remain, and little attention has been directed at examining the potential influence of TMS on AD pathogenesis. Our review briefly outlines some of the proposed neurobiological mechanisms of TMS benefits in AD, with particular emphasis on the modulatory effects on excitatory/inhibitory balance. On the basis of converging evidence from multiple fields, we caution that TMS therapeutic protocols established in young adults may have unexpected detrimental effects in older individuals or in the brain compromised by AD pathology. Our review surveys clinical studies of TMS in AD alongside basic research as a guide for moving this important area of work forward toward effective treatment development.

Navigated transcranial magnetic stimulation (nTMS) is increasingly applied to map human language functions. However, studies on protocol comparisons are mostly lacking. In this study, 20 healthy volunteers (25.7 ± 3.8 years, 12 females) underwent left-hemispheric language mapping by nTMS, combined with an object-naming task, over a cortical spot with reproducible naming errors within the triangular or opercular part of the inferior frontal gyrus (trIFG, opIFG: anterior stimulation) and the angular gyrus or posterior part of the superior temporal gyrus (anG, pSTG: posterior stimulation), respectively. Various stimulation intensities [80, 100, and 120% of the resting motor threshold (rMT)], frequencies (2, 5, 10, and 20 Hz), and coil orientations (in steps of 45°) were evaluated, and the adjustments leading to the highest error rates (ERs), combined with low occurrences of errors due to muscle stimulation, were considered optimal. Regarding anterior stimulation, 100% rMT, 5 Hz, and a coil orientation of 90° or 270° in relation to the respective stimulated gyrus resulted in optimal results. For posterior stimulation, 100% rMT, 10 Hz, and coil orientations of 90° or 270° were considered optimal. Errors due to facial muscle stimulation only played a considerable role during analyses of high-intensity (120% rMT) or high-frequency stimulation (20 Hz). In conclusion, this is one of the first studies to systematically investigate different stimulation protocols for nTMS language mapping, including detailed analyses of the distribution of ERs in relation to various coil orientations considered during neuronavigated stimulation. Mapping with 100% rMT, combined with 5 Hz (anterior stimulation) or 10 Hz (posterior stimulation) and a coil orientation perpendicular to the respective stimulated gyrus can be recommended as optimal adjustments.

Introduction: Conventional transcranial direct current stimulation (tDCS) and high-definition tDCS (HD-tDCS) may improve motor learning in children. Mechanisms are not understood. Neuronavigated robotic transcranial magnetic stimulation (TMS) can produce individualised maps of primary motor cortex (M1) topography. We aimed to determine the effects of tDCS- and HD-tDCS-enhanced motor learning on motor maps. Methods: Typically developing children aged 12-18 years were randomised to right M1 anodal tDCS, HD-tDCS, or Sham during training of their left-hand on the Purdue Pegboard Task (PPT) over 5 days. Bilateral motor mapping was performed at baseline (pre), day 5 (post), and 6-weeks retention time (RT). Primary muscle was the first dorsal interosseous (FDI) with secondary muscles of abductor pollicis brevis (APB) and adductor digiti minimi (ADM). Primary mapping outcomes were volume (mm2/mV) and area (mm2). Secondary outcomes were centre of gravity (COG, mm) and hotspot magnitude (mV). Linear mixed-effects modelling was employed to investigate effects of time and stimulation type (tDCS, HD-tDCS, Sham) on motor map characteristics. Results: Twenty-four right-handed participants (median age 15.5 years, 52% female) completed the study with no serious adverse events or dropouts. Quality maps could not be obtained in two participants. No effect of time or group were observed on map area or volume. LFDI COG (mm) differed in the medial-lateral plane (x-axis) between tDCS and Sham (p = 0.038) from pre-to-post mapping sessions. Shifts in map COG were also observed for secondary left-hand muscles. Map metrics did not correlate with behavioural changes. Conclusion: Robotic TMS mapping can safely assess motor cortex neurophysiology in children undergoing motor learning and neuromodulation interventions. Large effects on map area and volume were not observed while changes in COG may occur. Larger controlled studies are required to understand the role of motor maps in interventional neuroplasticity in children.

Two methods of non-invasive brain stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have demonstrable positive effects on cognition and can ameliorate neuropsychiatric symptoms such as depression. Less is known about the efficacy of these approaches in common neurodegenerative diseases. In this review, we evaluate the effects of TMS and tDCS upon cognitive and neuropsychiatric symptoms in the major dementias, including Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), and frontotemporal dementia (FTD), as well as the potential pre-dementia states of Mild Cognitive Impairment (MCI) and Parkinson's disease (PD).

Patients with advanced Parkinson's disease (PD) often receive deep brain stimulation (DBS) treatment, in which conductive leads are surgically implanted in the brain. While DBS treats tremor and rigidity, patients often continue to suffer from speech and swallowing impairments. There is preliminary evidence that transcranial magnetic stimulation (TMS) of the cortex may be beneficial for these symptoms. However, the potential electromagnetic interactions of the strong magnetic fields from TMS on the conductive leads is unknown, and the combination therapy has not been approved for use. In this article, we report an experimental study of the safety of combining DBS and TMS. We fabricated an anatomically accurate head and brain phantom with electrical conductivities matching cerebrospinal fluid and averaged conductivity of gray and white matter. Induced current on an implanted DBS probe in the brain phantom was measured. Our results show that TMS will induce current values in the range or higher than typical DBS stimulation current. Thus, the combination of TMS/DBS treatment might cause over-stimulation in the brain when stimulated directly over the DBS lead with 100% TMS current intensity.

Transcranial magnetic stimulation (TMS)-evoked phosphenes are oculocentric; their perceived location depends upon eye position. We investigated the accuracy and precision of TMS-evoked phosphene oculocentric mapping.