Epidural Cortical Stimulation Research Articles

Are invasive cortical stimulations effective in brain atrophy?

Electrical brain stimulation is a treatment method for brain disorder patients. The majority of patients with a severe brain disorder have brain atrophy. However, it is not clearly understood if electrical brain stimulation is effective even to brain atrophy. In this work, we developed anatomical head models with varying degrees of brain atrophy, so that we could investigate the effects of subdural/epidural cortical stimulations. The correlation between brain atrophy and cortical stimulation was quantified by calculating the effective volume that cortical stimulation influenced in this brain atrophy simulation study. The results showed that the effective volumes in both cortical stimulations decreased significantly with brain atrophy. There was also a strong correlation (0.9989) between the cerebrospinal fluid (CSF) and brain atrophy. The increase in CSF volume following brain atrophy reinforced the shunting effect between the brain and CSF and appeared to be the cause of a decrease in the stimulation effect on the brain. Overall, the epidural cortical stimulation was more sensitive (up to 57%) to the severity of the brain atrophy than the subdural cortical stimulation.

Invasive Neuromodulation Techniques for Treatment-Resistant Depression.

Surgically implanted neurostimulation devices for the treatment of depression have been studied for the last three decades. While the surgical risk associated with these treatment approaches clearly limits their use to the most severely impacted depressed patients, they offer a unique opportunity to better understand the impact of relatively localized alteration of neural activity in patient groups. As a result, these approaches provide a strict test of the role of individual neural structures or networks in mechanistic models of depression. In this chapter, we review the proposed mechanisms of action and evidence for clinical efficacy of vagal nerve stimulation, deep brain stimulation, and epidural cortical stimulation in patients with depression. The evidence for efficacy remains limited for all three modalities, but thelong-term follow-up studies of treated patients have highlighted the importance of interactions between neural regions in determining therapeutic response, and suggest that personalized approaches to stimulation are likely to be required.

Treatment-resistant depression. From classification to new therapies.

This paper aims to investigate the advances in recent years in the recognition and therapy of treatment-resistant depression starting from the concepts of: depressive disorder, resistance and pseudoresistance to drug treatment in depression, and appropriate treatments of treatment-resistant depression. An extensive research was carried out on scientific databases such as: PubMed, PsychInfo and Cochrane Library, until May 2022, using the keywords "major depression", "treatment-resistant depression", "staging", "instrumental therapies for resistant depression", "esketamine" and "psilocybin". Subjects who do not respond to antidepressants show a form of treatment resistance that requires an approach with additional pharmacological and/or instrumental therapies. Recently, esketamine and psilocybin are of particular interest among clinicians, and instrumental treatments such as: vagus nerve stimulation, deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, epidural cortical stimulation, and electro convulsive therapy, are being added to them. Treatment-resistant depression has increasingly become a public health problem due to the significant number of relapses, hospitalizations and mortality it entails, with increased demand for the use of more drugs, therapeutic resources by health services, and loss of quality of life for patients. Treatment-resistant depression needs to be addressed through the creation of dedicated study protocols. Future research should focus on the need to establish operational, valid and appropriate criteria, both on the psychopathological, clinical governance and therapeutic levels, focusing on the latest therapies in order to provide reliable data on the benefits, risks and costs associated with their use.

Feasibility of epidural temporal interference stimulation for minimally invasive electrical deep brain stimulation: simulation and phantom experimental studies

Objective. Temporal interference stimulation (TIS) has shown the potential as a new method for selective stimulation of deep brain structures in small animal experiments. However, it is challenging to deliver a sufficient temporal interference (TI) current to directly induce an action potential in the deep area of the human brain when electrodes are attached to the scalp because the amount of injection current is generally limited due to safety issues. Thus, we propose a novel method called epidural TIS (eTIS) to address this issue; in this method, the electrodes are attached to the epidural surface under the skull. Approach. We employed finite element method (FEM)-based electric field simulations to demonstrate the feasibility of eTIS. We first optimized the electrode conditions to deliver maximum TI currents to each of the three different targets (anterior hippocampus, subthalamic nucleus, and ventral intermediate nucleus) based on FEM, and compared the stimulation focality between eTIS and transcranial TIS (tTIS). Moreover, we conducted realistic skull-phantom experiments for validating the accuracy of the computational simulation for eTIS. Main results. Our simulation results showed that eTIS has the advantage of avoiding the delivery of TI currents over unwanted neocortical regions compared with tTIS for all three targets. It was shown that the optimized eTIS could induce neural action potentials at each of the three targets when a sufficiently large current equivalent to that for epidural cortical stimulation is injected. Additionally, the simulated results and measured results via the phantom experiments were in good agreement. Significance. We demonstrated the feasibility of eTIS, facilitating more focalized and stronger electrical stimulation of deep brain regions than tTIS, with the relatively less invasive placement of electrodes than conventional deep brain stimulation via computational simulation and realistic skull phantom experiments.

A narrative review on invasive brain stimulation for treatment-resistant depression.

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Rehabilitation of Upper Limb Motor Impairment in Stroke: A Narrative Review on the Prevalence, Risk Factors, and Economic Statistics of Stroke and State of the Art Therapies.

Stroke has been one of the leading causes of disability worldwide and is still a social health issue. Keeping in view the importance of physical rehabilitation of stroke patients, an analytical review has been compiled in which different therapies have been reviewed for their effectiveness, such as functional electric stimulation (FES), noninvasive brain stimulation (NIBS) including transcranial direct current stimulation (t-DCS) and transcranial magnetic stimulation (t-MS), invasive epidural cortical stimulation, virtual reality (VR) rehabilitation, task-oriented therapy, robot-assisted training, tele rehabilitation, and cerebral plasticity for the rehabilitation of upper extremity motor impairment. New therapeutic rehabilitation techniques are also being investigated, such as VR. This literature review mainly focuses on the randomized controlled studies, reviews, and statistical meta-analyses associated with motor rehabilitation after stroke. Moreover, with the increasing prevalence rate and the adverse socio-economic consequences of stroke, a statistical analysis covering its economic factors such as treatment, medication and post-stroke care services, and risk factors (modifiable and non-modifiable) have also been discussed. This review suggests that if the prevalence rate of the disease remains persistent, a considerable increase in the stroke population is expected by 2025, causing a substantial economic burden on society, as the survival rate of stroke is high compared to other diseases. Compared to all the other therapies, VR has now emerged as the modern approach towards rehabilitation motor activity of impaired limbs. A range of randomized controlled studies and experimental trials were reviewed to analyse the effectiveness of VR as a rehabilitative treatment with considerable satisfactory results. However, more clinical controlled trials are required to establish a strong evidence base for VR to be widely accepted as a preferred rehabilitation therapy for stroke.

Polarity dependent epicranial direct current stimulation over the cerebellum suppresses Harmaline tremor in rats

Abstract Background: Essential tremor (ET) is a neurological movement disorder that manifest a tremor in different body parts, but mainly the hands, leading to movement disability and social withdrawal. It is the most prevalent movement disorder with more than half of the patients not achieving satisfactory tremor reduction using medication. Thus, deep brain stimulation (DBS) becomes a standard treatment. However, DBS is highly invasive with stimulation electrodes being implanted in deep brain regions. To overcome that, the motor and the cerebellar cortex have been suggested as an alternative, more superficial, targets for stimulation. While results from an epidural cortical stimulation study were promising, this technique remains highly invasive requiring a craniotomy to implant the electrodes. Recently, we proposed a novel minimally invasive neuromodulation technique, epicranial current stimulation (ECS), that can deliver strong cortical current through subcutaneous electrodes. Here, we used Harmaline ET model in rats to test the ability of direct current epicranial current stimulation (DC-ECT) in reducing tremor. Methods: Rats were implanted with discrete epicranial electrodes placed over the motor cortices, the cerebellum and the frontal cortex. After surgery recovery, the rats were injected with Harmaline (15 mg/kg) to induce tremor which was measured using an accelerometer. Then DC-ECT was applied and different electrodes configurations were used to test the effects of stimulation on tremor suppression. Results: Our results show that DC-ECT suppresses Harmaline tremor in rats. Cerebellar stimulation showed a significant decrease in tremor compared to no stimulation. This effect was polarity dependent with anodal stimulation showing tremor reduction but not cathodal one. Conclusion: DC-ECT is a very promising neuromodulation technique that can suppress harmaline induced tremor in rats. Given its minimally invasive nature, it could be an alternative to DBS for ET patients. Keywords: epicranial stimulation, Essential tremor, Harmaline, Direct current stimulation

Computational exploration of epidural cortical stimulation using a realistic head model

Motor cortex stimulation, either non-invasively or with implanted electrodes, has been applied worldwide as a treatment for intractable neuropathic pain syndromes. Although computer simulations of non-invasive brain stimulation have been investigated largely to optimize protocols and improve our understanding of underlying mechanisms using a realistic head model, computational studies of invasive cortical stimulation are rare and limited to very simplified cortical models. In this paper, we present an anatomically realistic head model for epidural cortical stimulation that includes the most sophisticated epidural electrodes with an insulating paddle. The head model predicted the stimulus-induced field strengths according to two different stimulation techniques, bipolar and monopolar stimulations. We found that the stimulus-induced field focused on the precentral and postcentral gyri because of the epidural lead's invasiveness. Different stimulation configurations influenced the shape of the field markedly, and complex patterns of inward and outward directions of the radial field were observed in bipolar stimulation compared to those in monopolar stimulation. The spatial distributions of field strength showed that the optimal stimulation varied according to the target areas. In conclusion, we proposed an anatomically realistic head model and a sophisticated epidural lead to simulate epidural cortical stimulation-induced field strengths and identified the importance of such detailed modeling for epidural cortical stimulation because of the current's shunting through the cerebrospinal fluid.

A Review of Biological Interventions in Chronic Aphasia.

Aphasia is a common and debilitating condition following stroke. While the gold standard for aphasia treatment is behavioral speech-language therapy, benefits remain modest in chronic stages of recovery. This limitation motivates the pursuit of novel interventions for chronic aphasia. Here, we review biological approaches that have been used (or proposed for use, in the case of regenerative and genetic therapies) to treat chronic aphasia. These techniques aim to ameliorate the deficits of aphasia by directly manipulating brain function, rather than training lost or compensatory functions, although many have been used to augment effects of behavioral therapy. Specifically, we explore the most robust designs of transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and pharmacotherapy that have been applied in chronic (≥6 months) post-stroke aphasia. We also consider less investigated approaches including epidural cortical stimulation and photobiomodulation. All methods are currently in nascent phases and restricted to experimental studies and clinical trials. Although the evidence base remains limited, such interventions may ultimately improve language function and quality of life for those living with chronic aphasia. However, it is crucial that application of these methods consider the effects of concomitant speech-language therapy, as biological interventions combined with behaviorally induced experience-dependent plasticity will likely yield the most beneficial and durable outcomes.

Deep brain stimulation of the cerebellum for poststroke motor rehabilitation: from laboratory to clinical trial.

Ischemic stroke is a leading cause of disability worldwide, with profound economic costs. Poststroke motor impairment is the most commonly encountered deficit resulting in significant disability and is the primary driver of stroke-associated healthcare expenditures. Although many patients derive some degree of benefit from physical rehabilitation, a significant proportion continue to suffer from persistent motor impairment. Noninvasive brain stimulation, vagal nerve stimulation, epidural cortical stimulation, and deep brain stimulation (DBS) have all been studied as potential modalities to improve upon the benefits derived from physical therapy alone. These neuromodulatory therapies aim primarily to augment neuroplasticity and drive functional reorganization of the surviving perilesional cortex. The authors have proposed a novel and emerging therapeutic approach based on cerebellar DBS targeted at the dentate nucleus. Their rationale is based on the extensive reciprocal connectivity between the dentate nucleus and wide swaths of cerebral cortex via the dentatothalamocortical and corticopontocerebellar tracts, as well as the known limitations to motor rehabilitation imposed by crossed cerebellar diaschisis. Preclinical studies in rodent models of ischemic stroke have shown that cerebellar DBS promotes functional recovery in a frequency-dependent manner, with the most substantial benefits of the therapy noted at 30-Hz stimulation. The improvements in motor function are paralleled by increased expression of markers of synaptic plasticity, synaptogenesis, and neurogenesis in the perilesional cortex. Given the findings of preclinical studies, a first-in-human trial, Electrical Stimulation of the Dentate Nucleus Area (EDEN) for Improvement of Upper Extremity Hemiparesis Due to Ischemic Stroke: A Safety and Feasibility Study, commenced in 2016. Although the existing preclinical evidence is promising, the results of this Phase I trial and subsequent clinical trials will be necessary to determine the future applicability of this therapy.

Solenoidal Micromagnetic Stimulation Enables Activation of Axons With Specific Orientation.

Electrical stimulation of the central and peripheral nervous systems - such as deep brain stimulation, spinal cord stimulation, and epidural cortical stimulation are common therapeutic options increasingly used to treat a large variety of neurological and psychiatric conditions. Despite their remarkable success, there are limitations which if overcome, could enhance outcomes and potentially reduce common side-effects. Micromagnetic stimulation (μMS) was introduced to address some of these limitations. One of the most remarkable properties is that μMS is theoretically capable of activating neurons with specific axonal orientations. Here, we used computational electromagnetic models of the μMS coils adjacent to neuronal tissue combined with axon cable models to investigate μMS orientation-specific properties. We found a 20-fold reduction in the stimulation threshold of the preferred axonal orientation compared to the orthogonal direction. We also studied the directional specificity of μMS coils by recording the responses evoked in the inferior colliculus of rodents when a pulsed magnetic stimulus was applied to the surface of the dorsal cochlear nucleus. The results confirmed that the neuronal responses were highly sensitive to changes in the μMS coil orientation. Accordingly, our results suggest that μMS has the potential of stimulating target nuclei in the brain without affecting the surrounding white matter tracts.

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation

Objective. Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. Approach. ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. Main results. Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. Significance. Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

Comparison of Electrical and Ultrasound Neurostimulation in Rat Motor Cortex

Ultrasound (US) is known to non-invasively stimulate and modulate brain function; however, the mechanism of action is poorly understood. This study tested US stimulation of rat motor cortex (100 W/cm2, 200 kHz) in combination with epidural cortical stimulation. US directly evoked hindlimb movement. This response occurred even with short US bursts (3 ms) and had short latency (10 ms) and long refractory (3 s) periods. Unexpectedly, the epidural cortical stimulation hindlimb response was not altered during the 3-s refractory period of the US hindlimb response. This finding suggests that the US refractory period is not a general suppression of motor cortex, but rather the recovery time of a US-specific mechanism.

Epidural cortical stimulation for the treatment of chronic resistant tinnitus

Epidural cortical stimulation for the treatment of chronic resistant tinnitus

Developing and Evaluating a Flexible Wireless Microcoil Array Based Integrated Interface for Epidural Cortical Stimulation.

Stroke leads to serious long-term disability. Electrical epidural cortical stimulation has made significant improvements in stroke rehabilitation therapy. We developed a preliminary wireless implantable passive interface, which consists of a stimulating surface electrode, receiving coil, and single flexible passive demodulated circuit printed by flexible printed circuit (FPC) technique and output pulse voltage stimulus by inductively coupling an external circuit. The wireless implantable board was implanted in cats’ unilateral epidural space for electrical stimulation of the primary visual cortex (V1) while the evoked responses were recorded on the contralateral V1 using a needle electrode. The wireless implantable board output stable monophasic voltage stimuli. The amplitude of the monophasic voltage output could be adjusted by controlling the voltage of the transmitter circuit within a range of 5–20 V. In acute experiment, cortico-cortical evoked potential (CCEP) response was recorded on the contralateral V1. The amplitude of N2 in CCEP was modulated by adjusting the stimulation intensity of the wireless interface. These results demonstrated that a wireless interface based on a microcoil array can offer a valuable tool for researchers to explore electrical stimulation in research and the dura mater-electrode interface can effectively transmit electrical stimulation.

Array Focal Cortical Stimulation Enhances Motor Function Recovery and Brain Remodeling in a Rat Model of Ischemia

Using a new microelectrode array implanted into the cranial window employing a new stimulation protocol, we investigated the effects of the implanted electrode arrays on both motor map plasticity and neural regeneration in a rodent model of stroke. Rats were pretrained on single-pellet retrieval task, then received focal ischemic infarction and microelectrode arrays implantation. Rats in the cortical stimulation (CS) group received daily electrical stimulation (1 hour each day) for 14 days whereas animals in the no stimulation (NS) group did not receive electrical stimulation and only underwent motor mapping. Behavior data and residual electrophysiological mapping on stimulation days 2, 5, 8, 11, and 14 were statistically compared. Neural reorganization in pathological with glial fibrillary acidic protein and microtubule-associated protein-2 was performed. Rats in CS group showed greater increases in reaching accuracy and significantly decreased in motor threshold than rats in NS group. Immunohistochemical study has shown that array focal CS suppressed inflammatory response, and enhanced dendritic sprouting in the peri-infarction cortex. The present findings support the viability of epidural CS with microelectrode arrays for enhancing motor function after stroke and monitoring the neural reorganization of residual electrophysiological mapping after motor cortex injury.

EP 23. Bilateral epidural prefrontal cortical stimulation (EpCS) over fronto-polar and mid-frontal gyrus accesses mood regulation networks: Evidence from diffusion tensor imaging

Introduction The functional neuroanatomy of depression involves the prefrontal, cingulate and insular cortices, the amygdala, the nucleus accumbens and the hippocampus. The anterior and lateral prefrontal cortices are different in their cognitive and emotional integration roles and their modulation of sub-cortical regions. Both offer a distinct opportunity for targeted antidepressant treatments. Epidural prefrontal cortical stimulation (EpCS) is a unique therapeutic approach. It is more direct than transcranial magnetic stimulation (TMS) or vagus nerve stimulation (VNS), safer than deep brain stimulation (DBS) and, when applied chronically can reduce negative emotional arousal, increases stress tolerance and possibly lead to fewer relapses than observed with antidepressant pharmacotherapy Question Document the direct anatomical connections accessed with bilateral EpCS over fronto-polar and mid-frontal gyrus using diffusion tensor imaging (DTI). Methods Five patients treatment-resistant depression were implanted with bilateral EpCS leads over fronto-polar and mid-frontal gyrus. Patients underwent structural imaging (high resolution T1-weighted (T1w) MRI image and a DTI with 32 gradient directions) before surgery and a CT scan post-implantation. Image analysis was performed using the FMRIB Software Library. BA25, BA10 and BA46 areas, and Amygdala were extracted from the Broadmann area template to serve as guides for tractography. Similarly, individual EpCS paddles identified on CT scan were also transformed. First, an affine (12 parameter model) registration was applied to register Broadmann template onto T1w images and then T1w onto DTI data. Transformations were then applied to the guides. Second, a binary mask of the brain was extracted and applied to all images after correction for eddy currents. BedpostX was then run on the preprocessed data to generate the basis for probabilistic tractography using ProbtrackX. Estimation of tracts was done probabilistically, using a dual-fiber model with 5000 tract-following samples at each voxel. All tractography was done in each subject’s native space. Eight tractography combinations (left & right) were performed: BA10/BA46 as seeds for tractography and Amygdala/BA25 as waypoints masks. Similar approached was applied with EpCS actual lead masks. The resulting fibers were then thresholded at 0.01 (99% likelihood of connectivity) and then binarized, and transferred into MNI152 standard space for cross-subject analysis using a non-linear registration. To generate population-based probability fibers, all subjects’ individual fibers were added up and used as a basis for calculation of a mean image. Finally, the resulting mean fiber was thresholded to show voxels common to 80% or more of the subjects. Results All patients showed robust connections of different pathways in both left and right hemispheres. The resulting pathways connected to each seed combination are shown in Fig. 1 . Electrodes implanted over both BA10 and BA46 areas resulted in direct activation of axons that primarily project from BA10 or BA46 to BA25 and Amygdala, and extend to the cingulum bundle and to the middle occipital gyrus. Conclusion This is the first demonstration of EpCS direct anatomical access to the medial and lateral mood regulation networks. Encouraging clinical data have been reported elsewhere with 3 patients out of 5 showing remission at 7 months (Nahas et al., 2010) and at 5 years (Williams et al., under review). Bilateral anterior and lateral EpCS promises to be an innovative new treatment for a highly morbid disease through adaptive cortical governance of limbic structures but larger studies are needed.

Epidural Cortical Stimulation as Adjunctive Treatment for Nonfluent Aphasia

Background. There is increasing interest in the application of cortical stimulation (CS) as an adjuvant strategy in aphasia rehabilitation. Epidural CS, although more invasive than other methods, can provide high-frequency ipsilesional stimulation with greater spatial specificity. Objective. We review methods and results of a phase 1 study of epidural CS in combination with rehabilitation therapy in aphasia and provide new objective and self-report data collected between 6 and 21 months after the end of treatment. Methods. Eight stroke survivors with nonfluent aphasia received intensive language therapy, 3 hours a day, for 6 weeks. Four participants also underwent surgical implantation of an epidural stimulation device that was activated only during therapy sessions. Behavioral data were collected before treatment, at the end of treatment, and at 6 and 12 weeks after the end of treatment. Of the 8 participants, 7 also participated in the longer-term follow-up visit. Results. Changes in objective scores from baseline were larger in investigational participants than controls at all assessments, including the longer-term follow-up visit. Satisfaction ratings and ratings of overall improvement by investigational participants and their companions were more varied than those of the controls, but all indicated that they would recommend the investigational treatment to others with aphasia. Conclusions. Improvements were generally maintained for at least 12 weeks posttreatment and possibly as long as 21 months posttreatment. Epidural CS is a potentially safe, feasible adjunctive intervention for persons with chronic nonfluent aphasia that spares the ventral premotor cortex and warrants further investigation.

A transparent epidural electrode array for use in conjunction with optical imaging

BackgroundCombining optical imaging and direct cortical stimulation can be a powerful technique for high-resolution functional mapping of the cortex. However, stimulating electrodes often obstruct the field of view, resulting in a lack of functional images behind the electrodes. New methodTo overcome this problem, we developed a transparent electrode array with 16-contact grids for epidural cortical stimulation. Using a commercially available indium tin oxide (ITO)-coated polyethylene terephthalate (PET) sheet, the electrode array was fabricated using a photolithography process. Because a complete circuit pattern, including the electrode contact itself, was formed in the transparent metal ITO layer, our electrode array was completely transparent and therefore could be used with optical imaging. ResultsCortical stimulation was performed using the transparent electrode array. Evoked neural activity was successfully monitored through the array using a voltage-sensitive dye and optical imaging. The newly developed electrode array made it possible to detect optical signals from directly below the stimulating electrode. The electrode array could also be used for epidural recording of somatosensory evoked potentials. Comparison with existing methodsA variety of surface electrodes for cortical recording and stimulation exist. However, this study aimed to make electrodes as transparent as possible. We provided a simple and low-cost fabrication process for producing the transparent electrode arrays. ConclusionsOur transparent epidural electrode can be used for both stimulation and recordings without interfering with the detection of optical signals from the underlying cortex.

Brain Stimulation for Torsion Dystonia.

Dystonia is a heterogeneous neurologic disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly used. To review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation and to discuss recent advances relevant to patient selection, surgical approach, programming, and mechanism of action. PubMed was searched for publications on the clinical effect of brain stimulation in dystonia up through December 31, 2014. Recent meta-analyses, consensus statements, and evidence-based guidelines were incorporated. Emphasis was placed on deep brain stimulation (DBS) and randomized clinical trials; however, other stimulation modalities and trial designs were included. For each intervention the mean change in dystonia severity, number of patients studied, and evidence of efficacy based on American Academy of Neurology criteria were determined. Strong (level B) evidence supports the use of DBS for the treatment of primary generalized or segmental dystonia, especially when due to mutation in the DYT1 gene, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer's cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques, including epidural cortical stimulation and noninvasive brain stimulation, have been investigated, but generally report smaller effect sizes in fewer patients. Patients with dystonia that is not adequately controlled with standard medical therapy should be referred for consideration of DBS, especially patients with generalized, segmental, or cervical dystonia. Other less-invasive stimulation modalities require further research before being considered a therapeutic alternative.