Application of fMRI and Simultaneous fMRI-EEG Neurofeedback in Post-Stroke Motor Rehabilitation.

This article discusses the contribution of fMRI- and fMRI-EEG-neurofeedback into recovery of motor function in two subacute stroke patients during the early post-stroke period. Premotor and supplementary motor zones of the cortex were chosen as the targets of voluntary control. Patient 1 received 6 sessions of motor imagery-based fMRI neurofeedback of secondary motor areas activity and Patient 2 received a similar course with the addition of µ- and ß-EEG activity suppression. Both reduced the motor deficit severity, improved on the quality of life, and increased the C3/C4 coherence to other central leads within EEG µ-band. Patient 1 reliably increased the fMRI signal in target areas and improved on the strength and speed of hand movements. Patient 2 (fMRI-EEG) mastered the EEG activity regulation to a greater degree. The authors conclude that pure fMRI neurofeedback and bi-modal fMRI-EEG neurofeedback produce different clinical effects in motor rehabilitation, which confirms the prospect of the closed-loop stroke treatment.

A new device to improve target localization for transcranial magnetic stimulation therapy.

BACKGROUND: Accurate identification of cranial midline structures is essential for many targeting techniques that use repetitive transcranial magnetic stimulation (rTMS), including the Beam F3 method used for depression treatment. OBJECTIVE: Evaluate whether a novel, laser-sighted device will assist with more accurate identification of the cranial midline relative to standard scalp-based measurement procedures. METHODS: Three trained TMS technicians performed repeated scalp-based measurements to identify the inion and vertex on five subjects (n = 54 measurements). Measurements were compared to points identified with the midline localizer device and the true midline as defined by MRI midline structures. RESULTS: Use of the midline localizer was more accurate for midline identification than technician measurement (p = 0.00025) and the ratio of localizing the midline within 5 mm was higher (78% versus 54%, p = 0.008). CONCLUSION: Use of a laser-sighted midline localizer device can improve the accuracy of scalp measurements associated with target localization for rTMS treatment protocols.

Neuromodulation and Devices in Trigeminal Neuralgia.

PREMISE: Trigeminal neuralgia is a severe facial pain disorder that has been studied for decades. Classical trigeminal neuralgia (CTN) is either idiopathic or caused by neurovascular compression. The related painful trigeminal neuropathies are often secondary to other causes, such as multiple sclerosis or trauma. PROBLEM: Therapies for trigeminal neuralgia and neuropathy have often been pharmacologic or surgical. Pharmacologic therapies are not effective in some cases and often cause side effects, some substantial. Surgery can have comorbidity (such as anesthesia dolorosa, or painful differentiation of the affected nerve distribution) and also is not always effective. There is a desire, as in all chronic conditions, to find effective treatments with minimal morbidity and side effects. POTENTIAL SOLUTIONS: We review several devices including neuromodulation, ranging in invasiveness, for treatment of trigeminal neuralgia and neuropathy. We review existing data on sphenopalatine ganglion blocks, transcranial magnetic stimulation, transcortical direct stimulation, deep brain stimulation, spinal cord stimulation, peripheral nerve stimulation, and transcutaneous electrical stimulation for CTN and pain trigeminal neuropathies. We also offer hope for further research in this area with the goal of discovering a device that can provide treatment for many with few side effects and minimal morbidity.

Construction and Evaluation of Rodent-Specific rTMS Coils.

Rodent models of transcranial magnetic stimulation (TMS) play a crucial role in aiding the understanding of the cellular and molecular mechanisms underlying TMS induced plasticity. Rodent-specific TMS have previously been used to deliver focal stimulation at the cost of stimulus intensity (12 mT). Here we describe two novel TMS coils designed to deliver repetitive TMS (rTMS) at greater stimulation intensities whilst maintaining spatial resolution. Two circular coils (8 mm outer diameter) were constructed with either an air or pure iron-core. Peak magnetic field strength for the air and iron-cores were 90 and 120 mT, respectively, with the iron-core coil exhibiting less focality. Coil temperature and magnetic field stability for the two coils undergoing rTMS, were similar at 1 Hz but varied at 10 Hz. Finite element modeling of 10 Hz rTMS with the iron-core in a simplified rat brain model suggests a peak electric field of 85 and 12.7 V/m, within the skull and the brain, respectively. Delivering 10 Hz rTMS to the motor cortex of anaesthetized rats with the iron-core coil significantly increased motor evoked potential amplitudes immediately after stimulation (n = 4). Our results suggest these novel coils generate modest magnetic and electric fields, capable of altering cortical excitability and provide an alternative method to investigate the mechanisms underlying rTMS-induced plasticity in an experimental setting.

Potenciación del reaprendizaje motor y la recuperación funcional en pacientes con ictus: estrategias no invasivas de modulación del sistema nervioso central / Enhancement of motor relearning and functional recovery in stroke patients: non-invasive strategies for modulating the central nervous system

Introducción. La mayoría de los pacientes que han sufrido un ictus no recuperan el estado funcional basal de la extremidad superior afecta y sufren una grave limitación que permanece en la fase crónica de la enfermedad y que repercute de manera devastadora en su calidad de vida. Por ello, las estrategias de neurorrehabilitación tratan de evitar o minimizar las posibles disfunciones sensitivomotoras asociadas al ictus mediante la promoción de cambios plásticos en el sistema nervioso central. Desarrollo. La reorganización cerebral que tiene lugar tras el ictus puede promover la recuperación motora y funcional de los sujetos con ictus. No obstante, tras la lesión, también se pueden iniciar cambios neuroplásticos maladaptativos responsables del desarrollo de trastornos sensitivomotores, como el síndrome de espasticidad. Las estrategias no invasivas de estimulación cerebral, como la estimulación con corriente directa y la estimulación magnética transcraneal, son unas técnicas ampliamente utilizadas que, aplicadas sobre la corteza motora primaria, pueden modificar la excitabilidad de los circuitos neuronales y las funciones cognitivas, tanto en las personas sanas como en los pacientes con afectación neuroló- gica. Asimismo, los sistemas de interfaces cerebro-máquina también son capaces de generar esa reorganización por medio de la asociación contingente y simultánea entre la activación cerebral y la estimulación periférica. Conclusiones. Se evidencian los efectos positivos de las estrategias de neurorrehabilitación citadas previamente en la potenciación de la reorganización cortical después del ictus, así como en la paliación de los efectos adversos asociados al desarrollo de la espasticidad (AU)

Introduction. Most of the stroke survivors do not recover the basal state of the affected upper limb, suffering from a severe disability which remains during the chronic phase of the illness. This has an extremely negative impact in the quality of life of these patients. Hence, neurorehabilitation strategies aim at the minimization of the sensorimotor dysfunctions associated to stroke, by promoting neuroplasticity in the central nervous system. Development. Brain reorganization can facilitate motor and functional recovery in stroke subjects. Nonetheless, after the insult, maladaptive neuroplastic changes can also happen, which may lead to the appearance of certain sensorimotor disorders such as spasticity. Noninvasive brain stimulation strategies, like transcranial direct current stimulation or transcranial magnetic stimulation, are widely used techniques that, when applied over the primary motor cortex, can modify neural networks excitability, as well as cognitive functions, both in healthy subjects and individuals with neurological disorders. Similarly, brain-machine-interface systems also have the potential to induce a brain reorganization by the contingent and simultaneous association between the brain activation and the peripheral stimulation. Conclusion. This review describes the positive effects of the previously mentioned neurorehabilitation strategies for the enhancement of cortical reorganization after stroke, and how they can be used to alleviate the symptoms of the spasticity síndrome (AU)

The appropriate use of neurostimulation: stimulation of the intracranial and extracranial space and head for chronic pain. Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The International Neuromodulation Society (INS) has identified a need for evaluation and analysis of the practice of neurostimulation of the brain and extracranial nerves of the head to treat chronic pain. METHODS: The INS board of directors chose an expert panel, the Neuromodulation Appropriateness Consensus Committee (NACC), to evaluate the peer-reviewed literature, current research, and clinical experience and to give guidance for the appropriate use of these methods. The literature searches involved key word searches in PubMed, EMBASE, and Google Scholar dated 1970-2013, which were graded and evaluated by the authors. RESULTS: The NACC found that evidence supports extracranial stimulation for facial pain, migraine, and scalp pain but is limited for intracranial neuromodulation. High cervical spinal cord stimulation is an evolving option for facial pain. Intracranial neurostimulation may be an excellent option to treat diseases of the nervous system, such as tremor and Parkinson's disease, and in the future, potentially Alzheimer's disease and traumatic brain injury, but current use of intracranial stimulation for pain should be seen as investigational. CONCLUSIONS: The NACC concludes that extracranial nerve stimulation should be considered in the algorithmic treatment of migraine and other disorders of the head. We should strive to perfect targets outside the cranium when treating pain, if at all possible.

The appropriate use of neurostimulation: new and evolving neurostimulation therapies and applicable treatment for chronic pain and selected disease states. Neuromodulation Appropriateness Consensus Committee.

INTRODUCTION: The International Neuromodulation Society (INS) has determined that there is a need to provide an expert consensus that defines the appropriate use of neuromodulation technologies for appropriate patients. The Neuromodulation Appropriateness Consensus Committee (NACC) was formed to give guidance to current practice and insight into future developments. METHODS: The INS executive board selected members of the international scientific community to analyze scientific evidence for current and future innovations and to use clinical experience to fill in any gaps in information. The NACC used PubMed and Google Scholar to obtain current evidence in the field and used clinical and research experience to give a more complete picture of the innovations in the field. RESULTS: The NACC has determined that currently approved neurostimulation techniques and technologies have expanded our ability to treat patients in a more effective and specific fashion. Despite these advances, the NACC has identified several additional promising technologies and potential applications for neurostimulation that could move this field forward and expand the applicability of neuromodulation. CONCLUSIONS: The NACC concludes that the field of neurostimulation is an evolving and rapidly changing one that will lead to improved patient access, safety, and outcomes.

Magnetic fields in noninvasive brain stimulation.

The idea that magnetic fields could be used therapeutically arose 2000 years ago. These therapeutic possibilities were expanded after the discovery of electromagnetic induction by the Englishman Michael Faraday and the American Joseph Henry. In 1896, Arsène d'Arsonval reported his experience with noninvasive brain magnetic stimulation to the scientific French community. In the second half of the 20th century, changing magnetic fields emerged as a noninvasive tool to study the nervous system and to modulate neural function. In 1985, Barker, Jalinous, and Freeston presented transcranial magnetic stimulation, a relatively focal and painless technique. Transcranial magnetic stimulation has been proposed as a clinical neurophysiology tool and as a potential adjuvant treatment for psychiatric and neurologic conditions. This article aims to contextualize the progress of use of magnetic fields in the history of neuroscience and medical sciences, until 1985.

Transcranial magnetic stimulation and amyotrophic lateral sclerosis: pathophysiological insights.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons in the motor cortex, brainstem and spinal cord. A combination of upper and lower motor neuron dysfunction comprises the clinical ALS phenotype. Although the ALS phenotype was first observed by Charcot over 100 years ago, the site of ALS onset and the pathophysiological mechanisms underlying the development of motor neuron degeneration remain to be elucidated. Transcranial magnetic stimulation (TMS) enables non-invasive assessment of the functional integrity of the motor cortex and its corticomotoneuronal projections. To date, TMS studies have established motor cortical and corticospinal dysfunction in ALS, with cortical hyperexcitability being an early feature in sporadic forms of ALS and preceding the clinical onset of familial ALS. Taken together, a central origin of ALS is supported by TMS studies, with an anterograde transsynaptic mechanism implicated in ALS pathogenesis. Of further relevance, TMS techniques reliably distinguish ALS from mimic disorders, despite a compatible peripheral disease burden, thereby suggesting a potential diagnostic utility of TMS in ALS. This review will focus on the mechanisms underlying the generation of TMS measures used in assessment of cortical excitability, the contribution of TMS in enhancing the understanding of ALS pathophysiology and the potential diagnostic utility of TMS techniques in ALS.

Noninvasive transcranial focal stimulation via tripolar concentric ring electrodes lessens behavioral seizure activity of recurrent pentylenetetrazole administrations in rats.

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect.

Toward a noninvasive automatic seizure control system in rats with transcranial focal stimulations via tripolar concentric ring electrodes.

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study, we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback.

Noninvasive and invasive neuromodulation for the treatment of tinnitus: an overview.

OBJECTIVE: Nonpulsatile tinnitus is an auditory phantom percept characterized as a tone, or a noise-like sound such as a hissing or buzzing sound or polyphonic, in the absence of any objective physical sound source. Although advances have been made in symptomatic pharmacologic and nonpharmacologic treatments, these treatments are unable to eliminate the tinnitus sensation in most patients. A novel approach using noninvasive and invasive neuromodulation has emerged as an interesting and promising modality for tinnitus relief. METHODOLOGY: We review noninvasive neuromodulation techniques including transcranial magnetic stimulation, transcranial direct current stimulation, transcutaneous electrical nerve stimulation, and cortical neurofeedback, as well as invasive neuromodulation techniques including auditory cortex stimulation, dorsolateral prefrontal cortex stimulation, subcutaneous occipital nerve stimulation, and deep brain stimulation, as potential treatments of tinnitus. CONCLUSION: Although the different techniques introduced revealed promising results, further research is needed to better understand how these techniques work and how the brain responds to neuromodulation. More sophisticated stimulation regimens and parameters should be developed to dynamically stimulate various regions at different frequencies and intensities, physiologically tailored to the patient's brain state in an attempt to maximize efficacy.

Therapeutic devices for epilepsy.

Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation (VNS), which continues to develop new technology, is approved for use in the United States. Deep brain stimulation of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to 1 or 2 seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS are split on efficacy, which may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of shake detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of electroencephalography (EEG) is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures, and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience.

Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices.

BACKGROUND: The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. METHODS: This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. RESULTS: The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation. CONCLUSIONS: We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated.

Combined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: an exploratory, randomized multicenter trial.

BACKGROUND: No rehabilitation intervention has effectively improved functional use of the arm and hand in patients with severe upper limb paresis after stroke. Pilot studies suggest the potential for transcranial direct current stimulation and bilateral robotic training to enhance gains. OBJECTIVE: In a double-blind, randomized trial the combination of these interventions was tested. METHODS: This study randomized 96 patients with an ischemic supratentorial lesion of 3 to 8 weeks' duration with severe impairment of motor control with a Fugl-Meyer score (FMS) for the upper limb <18 into 3 groups. For 6 weeks, group A received anodal stimulation of the lesioned hemisphere, group B received cathodal stimulation of the nonlesioned side for 20 minutes at 2.0 mA, and group C received sham stimulation. The electrodes were placed over the hand area and above the contralateral orbit. Contemporaneously, the subjects practiced 400 repetitions each of 2 different bilateral movements on a robotic assistive device. RESULTS: The groups were matched at onset. The FMS improved in all patients at 6 weeks (P < .001). No between-group differences were found; initial versus finish FMS scores were 7.8 ± 3.8 versus 19.1 ± 14.4 in group A, 7.9 ± 3.4 versus 18.8 ± 10.5 in group B, and 8.2 ± 4.4 versus 19.2 ± 15.0 in group C. No significant changes between groups were present at 3 months. CONCLUSIONS: Neither anodal nor cathodal transcranial direct current stimulation enhanced the effect of bilateral arm training in this exploratory trial of patients with cortical involvement and severe weakness. Unilateral hand training and upregulation of the nonlesioned hemisphere might also be tried in this population.

[The effectiveness of transcranial treatment using the AMO-ATOS-E apparatus for the correction of the reproductive system disorders in adolescent girls].

A combination of transcranial therapy and transcranial electrostimulation based on the use of the AMO-ATOS-E apparatus was applied to elucidate the hormonal status and to study lipid and carbohydrate metabolism in 84 girls of pubertal age. The correction of menstrual cycles in these patients brought about its normalization in 86.3% of the cases with the simultaneous reduction of their body weight by 9.26 +/- 4.28 kg during 3 months.

Noninvasive transcranial brain stimulation and pain.

Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two noninvasive brain stimulation techniques that can modulate activity in specific regions of the cortex. At this point, their use in brain stimulation is primarily investigational; however, there is clear evidence that these tools can reduce pain and modify neurophysiologic correlates of the pain experience. TMS has also been used to predict response to surgically implanted stimulation for the treatment of chronic pain. Furthermore, TMS and tDCS can be applied with other techniques, such as event-related potentials and pharmacologic manipulation, to illuminate the underlying physiologic mechanisms of normal and pathological pain. This review presents a description and overview of the uses of two major brain stimulation techniques and a listing of useful references for further study.

Consensus: New methodologies for brain stimulation.

We briefly summarized several new stimulation techniques. There are many new methods of human brain stimulation, including modification of already known methods and brand-new methods. In this article, we focused on theta burst stimulation (TBS), repetitive monophasic pulse stimulation, paired- and quadri-pulse stimulation, transcranial alternating current stimulation (tACS), paired associative stimulation, controllable pulse shape TMS (cTMS), and deep-brain TMS. For every method, we summarized the state of the art and discussed issues that remain to be addressed.