Dietary curcumin counteracts the outcome of traumatic brain injury on oxidative stress, synaptic plasticity, and cognition

The pervasive action of oxidative stress on neuronal function and plasticity after traumatic brain injury (TBI) is becoming increasingly recognized. Here, we evaluated the capacity of the powerful antioxidant curry spice curcumin ingested in the diet to counteract the oxidative damage encountered in the injured brain. In addition, we have examined the possibility that dietary curcumin may favor the injured brain by interacting with molecular mechanisms that maintain synaptic plasticity and cognition. The analysis was focused on the BDNF system based on its action on synaptic plasticity and cognition by modulating synapsin I and CREB. Rats were exposed to a regular diet or a diet high in saturated fat, with or without 500 ppm curcumin for 4 weeks (n = 8/group), before a mild fluid percussion injury (FPI) was performed. The high-fat diet has been shown to exacerbate the effects of TBI on synaptic plasticity and cognitive function. Supplementation of curcumin in the diet dramatically reduced oxidative damage and normalized levels of BDNF, synapsin I, and CREB that had been altered after TBI. Furthermore, curcumin supplementation counteracted the cognitive impairment caused by TBI. These results are in agreement with previous evidence, showing that oxidative stress can affect the injured brain by acting through the BDNF system to affect synaptic plasticity and cognition. The fact that oxidative stress is an intrinsic component of the neurological sequel of TBI and other insults indicates that dietary antioxidant therapy is a realistic approach to promote protective mechanisms in the injured brain.     

Transcranial magnetic stimulation and neuroplasticity

We review past results and present novel data to illustrate different ways in which TMS can be used to study neural plasticity. Procedural learning during the serial reaction time task (SRTT) is used as a model of neural plasticity to illustrate the applications of TMS. These different applications of TMS represent principles of use that we believe are applicable to studies of cognitive neuroscience in general and exemplify the great potential of TMS in the study of brain and behavior. We review the use of TMS for (1) cortical output mapping using focal, single-pulse TMS; (2) identification of the mechanisms underlying neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the information of other neuroimaging techniques by transient disruption of cortical function using repetitive TMS; and finally (4) modulation of cortical function with repetitive TMS to influence behavior and guide plasticity.     

Things you wanted to know (but might have been afraid to ask) about how and why to explore and modulate brain plasticity with non-invasive neurostimulation technologies

Brain plasticity can be defined as the ability of local and extended neural systems to organize either the structure and/or the function of their connectivity patterns to better adapt to changes of our inner/outer environment and optimally respond to new challenging behavioral demands. Plasticity has been traditionally conceived as a spontaneous phenomenon naturally occurring during pre and postnatal development, tied to learning and memory processes, or enabled following neural damage and their rehabilitation. Such effects can be easily observed and measured but remain hard to harness or to tame ‘at will’. Non-invasive brain stimulation (NIBS) technologies offer the possibility to engage plastic phenomena, and use this ability to characterize the relationship between brain regions, networks and their functional connectivity patterns with cognitive process or disease symptoms, to estimate cortical malleability, and ultimately contribute to neuropsychiatric therapy and rehabilitation. NIBS technologies are unique tools in the field of fundamental and clinical research in humans. Nonetheless, their abilities (and also limitations) remain rather unknown and in the hands of a small community of experts, compared to widely established methods such as functional neuroimaging (fMRI) or electrophysiology (EEG, MEG). In the current review, we first introduce the features, mechanisms of action and operational principles of the two most widely used NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Current Stimulation (tCS), for exploratory or therapeutic purposes, emphasizing their bearings on neural plasticity mechanisms. In a second step, we walk the reader through two examples of recent domains explored by our team to further emphasize the potential and limitations of NIBS to either explore or improve brain function in healthy individuals and neuropsychiatric populations. A final outlook will identify a series of future topics of interest that can foster progress in the field and achieve more effective manipulation of brain plasticity and interventions to explore and improve cognition and treat the symptoms of neuropsychiatric diseases.     

Biophysical modeling of neural plasticity induced by transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method capable of inducing plastic reorganisation of cortical circuits in humans. Changes in neural activity following TMS are often attributed to synaptic plasticity via process of long-term potentiation and depression (LTP/LTD). However, the precise way in which synaptic processes such as LTP/LTD modulate the activity of large populations of neurons, as stimulated en masse by TMS, are unclear. The recent development of biophysical models, which incorporate the physiological properties of TMS-induced plasticity mathematically, provide an excellent framework for reconciling synaptic and macroscopic plasticity. This article overviews the TMS paradigms used to induce plasticity, and their limitations. It then describes the development of biophysically-based numerical models of the mechanisms underlying LTP/LTD on population-level neuronal activity, and the application of these models to TMS plasticity paradigms, including theta burst and paired associative stimulation. Finally, it outlines how modeling can complement experimental work to improve mechanistic understandings and optimize outcomes of TMS-induced plasticity.     

A new device and protocol for combining TMS and online recordings of EEG and evoked potentials

We describe an electroencephalographic (EEG) device and protocol that allows recording of electrophysiological signals generated by the human brain during transcranial magnetic stimulation (TMS) despite the TMS-induced high-voltage artifacts. The key hardware components include slew-rate limited preamplifiers to prevent saturation of the EEG system due to TMS. The protocol involves artifact subtraction to isolate the electrophysiological signals from residual TMS-induced contaminations. The TMS compatibility of the protocol is illustrated with examples of two data sets demonstrating the feasibility of the approach in the single-pulse TMS design, as well as during repetitive TMS. Our data show that both high-amplitude potentials evoked by visual checkerboard stimulation and low-amplitude steady-state oscillations induced by auditory click-trains can be retrieved with the present protocol. The signals recorded during TMS perfectly matched control EEG responses to the same visual and auditory stimuli. The main field of application of the present protocol is in cognitive neuroscience complementing behavioral studies that use TMS to induce transient, 'virtual lesions'. Combined EEG-TMS techniques provide neuroscientists with a unique method to test hypothesis on functional connectivity, as well as on mechanisms of functional orchestration, reorganization, and plasticity.     

Transcranial magnetic stimulation in cognition and neuropsychology

Classical neuropsychology relies on patients with irreversible brain lesions and cognitive impairments give informations about normal brain function. Transcranial Magnetic Stimulation (TMS) is a non-invasive method which involves placing an electromagnetic coil on the scalp. A pulse generates a magnetic field and this one passes, unattenuated by the skin and scalp, into the cortex inducing a current which results in neural activity. The technique shows a good temporal resolution and, moreover, because it represents an interference technique, can be said to have excellent functional resolution. For this reason, TMS appears to be a new tool for research in neuropsychology, producing transitory 'virtual lesion'effects which could help to understand how, when and where cognitive tasks are performed. The purpose of this article is to review recent research using TMS in cognition and neuropsychology, in a non exhaustive way. In safety studies, single TMS over motor cortex can produce simple movements. Several groups have applied TMS to the study of visual processing and found an impaired detection of visual stimuli. In a same way, TMS can disrupt speech when it was delivered in the language dominant hemisphere. Studies on the memory effects of TMS have been conflicting and the results seem to depend on the choice of paradigm and parameters. Other study depicted improvements in executive functioning after TMS on the left middle frontal gyrus or a diminution in reaction time during an analogic reasoning task. Moreover, some facial emotions seem to be less recognizable after TMS. Although TMS seem to be a new tool for neuro-psychological investigations in healthy subjects, few studies reported cognitive effects of rTMS treatment in psychiatry. In a therapeutic view, many of these trials have supported a significant effect of TMS, but in some studies the effect is small and short lived. Several groups have reported on the use of rTMS as a treatment in resistant major depression and the impact on cognition functioning. Most of results tend to find no adverse cognitive effects after several weeks of daily rTMS in depressed patients, compared to Electroconvulsivo-therapy (ECT). The effects of transcranial magnetic stimulation (TMS) on hallucination severity and neurocognition were studied in a recent study. A statistically significant improvement was observed on a hallucination scale and on one cognitive measure. TMS is a promising tool for cognitive neuroscience and can provide complementary information to the one obtained using neuropsychological tests, and the one obtained using functional imaging techniques, which have superior spatial but inferior temporal resolution.     

Diagnostic contribution and therapeutic perspectives of transcranial magnetic stimulation in dementia

Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such as excitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of the pathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention.The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment.To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer’s disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression.In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.     

Neue Einblicke in die Hirnfunktion durch Kombination von transkranieller magnetischer Kortexstimulation und funktioneller zerebraler Bildgebung

The present paper aims to summarize potential applications of transcranial magnetic stimulation (TMS) combined with functional brain imaging. Transcranial magnetic stimulation is a well-established noninvasive tool for stimulating circumscribed areas of the human cortex. Functional imaging techniques such as positron emission tomography, functional magnetic resonance imaging, and electroencephalographic mapping enable assessment of TMS-related functional brain activation. A combination of TMS and functional imaging can be useful in three principal ways. (1) Brain imaging before TMS is helpful in defining the accurate coil position over a distinct cortical area which is targeted by TMS. Since TMS can be used to interfere with regional cortical function during a given task, the effects of focal TMS on task performance can help to clarify the task-specific functional contribution of a given cortical area which has previously shown task-related activation in a functional imaging study. (2) Imaging the brain during TMS is a promising approach for assessing cortical excitability and intracerebral functional connectivity. (3) By evaluating lasting effects of TMS, brain imaging after TMS can be employed to study the plasticity of the human cortex. Moreover, this approach will help to advance our understanding of therapeutical effects related to TMS.     

Plasticity of the visual system after early brain damage

The aim of this review is to discuss the existing evidence supporting different processes of visual brain plasticity after early damage, as opposed to damage that occurs during adulthood. There is initial evidence that some of the neuroplastic mechanisms adopted by the brain after early damage to the visual system are unavailable at a later stage. These are, for example, the ability to differentiate functional tissue within a larger dysplastic cortex during its formation, or to develop new thalamo‐cortical connections able to bypass the lesion and reach their cortical destination in the occipital cortex. The young brain also uses the same mechanisms available at later stages of development but in a more efficient way. For example, in people with visual field defects of central origin, the anatomical expansion of the extrastriatal visual network is greater after an early lesion than after a later one, which results in more efficient mechanisms of visual exploration of the blind field. A similar mechanism is likely to support some of the differences found in people with blindsight, the phenomenon of unconscious visual perception in the blind field. In particular, compared with people with late lesions, those with early brain damage appear to have stronger subjective awareness of stimuli hitting the blind visual field, reported as a conscious feeling that something is present in the visual field. Expanding our knowledge of these mechanisms could help the development of early therapeutic interventions aimed at supporting and enhancing visual reorganization at a time of greatest potential brain plasticity.     

Transcranial magnetic stimulation. A case report and review of the literature

OBJECTIVE: Transcranial magnetic stimulation (TMS) is a non-invasive tool for the electrical stimulation of neural tissue. TMS can be applied as single pulses of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies. CASE REPORT: A 2-years-old male infant was referred to our department with a history of Epstein-Barr virus (EBV) encephalitis, treated with foscarnet and steroids, for he developed mutism and ataxia and loss of the ability to eat, walk and talk. Brain imaging revealed loss of white matter around ventricles and progressive global brain atrophy, findings consistent with encephalopathy. Serology for antibodies against EBV infection was positive and the diagnosis of acute and prolonged EBV infection was made. There was an improvement of the clinical findings after the application of TMS with proper field characteristics (intensity: 1-7.5 pT, frequency: 8-13 Hz). CONCLUSIONS: Our case illustrates the possibility of therapeutic applications of TMS (in the order of pT) with proper field characteristics to normalize pathologically decreased levels of brain cortex activity. TMS might provide novel insights into the pathophysiology of the neural circuitry, be developed into clinically useful diagnostic and prognostic tests, and have therapeutic uses in various diseases.     

Transcranial magnetic stimulation (TMS)/repetitive TMS in mild cognitive impairment and Alzheimer's disease

Several Transcranial Magnetic Stimulation (TMS) techniques can be applied to noninvasively measure cortical excitability and brain plasticity in humans. TMS has been used to assess neuroplastic changes in Alzheimer's disease (AD), corroborating findings that cortical physiology is altered in AD due to the underlying neurodegenerative process. In fact, many TMS studies have provided physiological evidence of abnormalities in cortical excitability, connectivity, and plasticity in patients with AD. Moreover, the combination of TMS with other neurophysiological techniques, such as high‐density electroencephalography (EEG), makes it possible to study local and network cortical plasticity directly. Interestingly, several TMS studies revealed abnormalities in patients with early AD and even with mild cognitive impairment (MCI), thus enabling early identification of subjects in whom the cholinergic degeneration has occurred. Furthermore, TMS can influence brain function if delivered repetitively; repetitive TMS (rTMS) is capable of modulating cortical excitability and inducing long‐lasting neuroplastic changes. Preliminary findings have suggested that rTMS can enhance performances on several cognitive functions impaired in AD and MCI. However, further well‐controlled studies with appropriate methodology in larger patient cohorts are needed to replicate and extend the initial findings. The purpose of this paper was to provide an updated and comprehensive systematic review of the studies that have employed TMS/rTMS in patients with MCI and AD.     

Brain functional reorganization in children with hemiplegic cerebral palsy: Assessment with TMS and therapeutic perspectives

Transcranial magnetic stimulation (TMS) can be a useful tool for the assessment of the brain functional reorganization in subjects with hemiplegic cerebral palsy (HCP). In this review, we performed a systematic search of all studies using TMS in order to explore the neuroplastic changes that occur in HCP patients. We aimed at investigating the usefulness of TMS to explore cortical excitability, plasticity and connectivity changes in HCP. Children with HCP due to unilateral lesions of the corticospinal system had ipsilateral motor evoked potentials (MEPs) similar to those recorded contralaterally. TMS studies demonstrated that occupational and constraint-induced movement therapy were associated with significant improvements in contralateral and ipsilateral corticomotor projection patterns. In addition, after intensive bimanual therapy, children with HCP showed increased activation and size of the motor areas controlling the affected hand. A TMS mapping study revealed a mediolateral location of the upper and lower extremity map motor cortical representations. Deficits in intracortical and interhemispheric inhibitory mechanisms were observed in HCP. Early hand function impairment correlated with the extension of brain damage, number of involved areas, and radiological signs of corticospinal tract (CST) degeneration. Clinical mirror movements (MMs) correlated with disability and CST organization in subjects with HCP and a positive relationship was found between MMs and MEPs strength. Therefore, TMS studies have shed light on important pathophysiological aspects of motor cortex and CST reorganization in HCP patients. Furthermore, repetitive TMS (rTMS) might have therapeutic effects on CST activities, functional connectivity and clinical status in children with HCP.     

Transcranial magnetic stimulation and motor plasticity in human lateral cerebellum: dual effect on saccadic adaptation

The cerebellum is a key area for movement control and sensory-motor plasticity. Its medial part is considered as the exclusive cerebellar center controlling the accuracy and adaptive calibration of saccadic eye movements. However, the contribution of other zones situated in its lateral part is unknown. We addressed this question in healthy adult volunteers by using magnetic resonance imaging (MRI)-guided transcranial magnetic stimulation (TMS). The double-step target paradigm was used to adaptively lengthen or shorten saccades. TMS pulses over the right hemisphere of the cerebellum were delivered at 0, 30, or 60 ms after saccade detection in separate recording sessions. The effects on saccadic adaptation were assessed relative to a fourth session where TMS was applied to Vertex as a control site. First, TMS applied upon saccade detection before the adaptation phase reduced saccade accuracy. Second, TMS applied during the adaptation phase had a dual effect on saccadic plasticity: adaptation after-effects revealed a potentiation of the adaptive lengthening and a depression of the adaptive shortening of saccades. For the first time, we demonstrate that TMS on lateral cerebellum can influence plasticity mechanisms underlying motor performance. These findings also provide the first evidence that the human cerebellar hemispheres are involved in the control of saccade accuracy and in saccadic adaptation, with possibly different neuronal populations concerned in adaptive lengthening and shortening. Overall, these results require a reappraisal of current models of cerebellar contribution to oculomotor plasticity.     

Extinguishing extinction: hemispheric differences in the modulation of TMS-induced visual extinction by directing covert spatial attention

The topic of spatial attention is of great relevance for researchers in various fields, including neuropsychology, cognitive neuroscience, and cognitive psychology, as well as for clinical practice. Deficits of spatial attentional arising from parietal brain damage remain largely confined to the left visual field. The mechanisms underlying this hemispheric asymmetry are still elusive. We mimicked the neuropsychological syndrome of contralesional extinction by temporarily inducing a spatial attentional bias in healthy volunteers with TMS. We investigated whether directing covert spatial attention could enhance or, more importantly, counteract the resulting behavioral deficits. Although both the left and right parietal TMS induced contralateral extinction, only left hemifield extinction following right parietal TMS was severely aggravated by a competing stimulus in the ipsilesional (right) hemifield. We put forward the hypothesis that an asymmetry with respect to the ability of detaching attention from a distractor is contributing to the right hemispheric lateralization with regard to extinction. On a broader level, we suggest that "virtual patients" might be used for evaluating neuropsychological treatment in an early stage of development, reducing the burden on actual patients.     

TMS-EEG co-registration: On TMS-induced artifact

ObjectiveThe combination of brain stimulation by transcranial magnetic stimulation (TMS) and simultaneous electroencephalographic (EEG) recording has the potential to be of great value for understanding human brain functions. Recording EEG during TMS can be technically challenging because TMS induces a very strong electrical field that can saturate recording amplifiers for a long duration. Advances in amplifier technology, however, have led to the development of TMS-compatible EEG equipment that can work in very high, time-varying magnetic fields without saturation. The aim of the present study was to identify stimulus-related artifacts, and to provide experimental data containing the length of the artifact induced by the magnetic field and its variations with respect to the experimental setting.MethodsA phantom head was stimulated to record the artifact while excluding cortical responses. We tested different types of electrodes, coils, models of stimulator, and frequencies and intensities of stimulation to see how these parameters influence the duration of the artifact.ResultsThe electrical artifact produced by the magnetic pulse lasted approximately 5 ms following TMS onset. Its length was invariant irrespective of different experimental conditions.ConclusionsThese data suggest that it is possible to analyze the cortical evoked response induced by TMS 5 ms after TMS onset.SignificanceThe possibility to study the early physiological responses to TMS stimulation may have valuable implications for both clinical and experimental purposes, providing information about the early direct cortical response of the stimulated areas.     

Transcranial magnetic stimulation in psychiatry: research and therapeutic applications

Transcranial magnetic stimulation (TMS) is a new, non-invasive procedure where a localized pulsed magnetic field to the surface of the head depolarizes underlying superficial neurons. The magnetic field is generated by passing powerful, brief electrical currents through a conducting coil, held close to the scalp. This electrically generated magnetic field passes unimpeded through the skull (transcranial) and is focused in the cortex (stimulation). The earliest research uses of TMS were in neurology, where TMS was used to examine central and peripheral nerve conduction as well as to study motor cortex. More recently, this technology has been widely used to map various brain functions such as visual information processing, language, memory, emotion, and movement. The ability to excite or inhibit local areas of the brain has raised the possibility of whether TMS might be a novel therapeutic tool for various psychiatric disorders. Here we review the methodology of TMS and its emerging research and therapeutic applications in psychiatry.     

Real-time estimation of electric fields induced by transcranial magnetic stimulation with deep neural networks

BackgroundTranscranial magnetic stimulation (TMS) plays an important role in treatment of mental and neurological illnesses, and neurosurgery. However, it is difficult to target specific brain regions accurately because the complex anatomy of the brain substantially affects the shape and strength of the electric fields induced by the TMS coil. A volume conductor model can be used for determining the accurate electric fields; however, the construction of subject-specific anatomical head structures is time-consuming.ObjectiveThe aim of this study is to propose a method to estimate electric fields induced by TMS from only T1 magnetic resonance (MR) images, without constructing a subject-specific anatomical model.MethodsVery large sets of electric fields in the brain of subject-specific anatomical models, which are constructed from T1 and T2 MR images, are computed by a volume conductor model. The relation between electric field distribution and T1 MR images is used for machine learning. Deep neural network (DNN) models are applied for the first time to electric field estimation.ResultsBy determining the relationships between the T1 MR images and electric fields by DNN models, the process of electric field estimation is markedly accelerated (to 0.03 s) due to the absence of a requirement for anatomical head structure reconstruction and volume conductor computation. Validation shows promising estimation accuracy, and rapid computations of the DNN model are apt for practical applications.ConclusionThe study showed that the DNN model can estimate the electric fields from only T1 MR images and requires low computation time, suggesting the possibility of using machine learning for real-time electric field estimation in navigated TMS.     

The contribution of transcranial magnetic stimulation in the diagnosis and in the management of dementia

Transcranial magnetic stimulation (TMS) is emerging as a promising tool to non-invasively assess specific cortical circuits in neurological diseases. A number of studies have reported the abnormalities in TMS assays of cortical function in dementias. A PubMed-based literature review on TMS studies targeting primary and secondary dementia has been conducted using the key words “transcranial magnetic stimulation” or “motor cortex excitability” and “dementia” or “cognitive impairment” or “memory impairment” or “memory decline”. Cortical excitability is increased in Alzheimer’s disease (AD) and in vascular dementia (VaD), generally reduced in secondary dementias. Short-latency afferent inhibition (SAI), a measure of central cholinergic circuitry, is normal in VaD and in frontotemporal dementia (FTD), but suppressed in AD. In mild cognitive impairment, abnormal SAI may predict the progression to AD. No change in cortical excitability has been observed in FTD, in Parkinson’s dementia and in dementia with Lewy bodies. Short-interval intracortical inhibition and controlateral silent period (cSP), two measures of gabaergic cortical inhibition, are abnormal in most dementias associated with parkinsonian symptoms. Ipsilateral silent period (iSP), which is dependent on integrity of the corpus callosum is abnormal in AD. While single TMS measure owns low specificity, a panel of measures can support the clinical diagnosis, predict progression and possibly identify earlier the “brain at risk”. In dementias, TMS can be also exploited to select and evaluate the responders to specific drugs and, it might become a rehabilitative tool, in the attempt to restore impaired brain plasticity.     

Care for child development: basic science rationale and effects of interventions

The past few years have witnessed increasing interest in devising programs to enhance early childhood development. We review current understandings of brain development, recent advances in this field, and their implications for clinical interventions. An expanding body of basic science laboratory data demonstrates that several interventions, including environmental enrichment, level of parental interaction, erythropoietin, antidepressants, transcranial magnetic stimulation, transcranial direct current stimulation, hypothermia, nutritional supplements, and stem cells, can enhance cerebral plasticity. Emerging clinical data, using functional magnetic resonance imaging and clinical evaluations, also support the hypothesis that clinical interventions can increase the developmental potential of children, rather than merely allowing the child to achieve an already predetermined potential. Such interventions include early developmental enrichment programs, which have improved cognitive function; high-energy and high-protein diets, which have increased brain growth in infants with perinatal brain damage; constraint-induced movement therapy, which has improved motor function in patients with stroke, cerebral palsy, and cerebral hemispherectomy; and transcranial magnetic stimulation, which has improved motor function in stroke patients.     

Basic mechanisms of TMS.

Transcranial magnetic stimulation (TMS) is now established as an important noninvasive measure for neurophysiologic investigation of the central and peripheral nervous systems in humans. Magnetic stimulation can be used for stimulating peripheral nerves with a similar mechanism of activation as for electrical stimulation. When TMS is applied to the cerebral cortex, however, some features emerge that distinguish it from transcranial electrical stimulation. One of the most important features is designated the D and I wave hypothesis, which is now widely accepted as a mechanism of TMS of the motor cortex. Transcranial electrical stimulation excites the pyramidal tract axons directly, either at the initial segment of the neuron or at proximal internodes in the subcortical white matter, giving rise to D (direct) waves, whereas TMS excites the pyramidal neurons transsynaptically, giving rise to I (indirect) waves. There are still other phenomena with mechanisms that remain to be elucidated. First, not only excitatory effects but also inhibitory effects can be elicited by TMS of the cerebral cortex (e.g., the silent period and intracortical inhibition). The inhibitory effect may also be used to investigate cerebral functions other than the motor cortex, such as the visual, sensory cortices, and the frontal eye field, from which no overt response like the motor evoked potential can be elicited. Second, there is an abundance of intraregional functional connectivities among different cortical areas that can also be revealed by TMS, or TMS in combination with neuroimaging techniques. Last, repetitive transcranial stimulation exerts a lasting effect on brain function even after the stimulation has ceased. With further investigation of the neural mechanisms of TMS, these techniques will open up new possibilities for investigating the physiologic function of the brain as well as opportunities for clinical application.