Brain Electrodes Research Articles

Changes in tissue oxygen tension, venous saturation, and Fick-based assessments of cardiac output during hyperoxia.

Hyperoxemia (arterial oxygen tension >100mmHg) may occur in critically ill patients and have effects on mixed venous saturation (SvO2 ) and on Fick-based estimates of cardiac output (CO). We investigated the effect of hyperoxemia on SvO2 and on assessments of CO using the Fick equation. Yorkshire swine (n=14) were anesthetized, intubated, and paralyzed for instrumentation. SvO2 (co-oximetry) and tissue oxygen tension (tPO2 , implantable electrodes) in brain and myocardium were measured during systematic manipulation of arterial oxygen tension (PaO2 ) using graded hyperoxia (fraction of inspired oxygen 0.21 → 0.8). Secondarily, oxygen- and carbon dioxide-based estimates of CO (FickO2 and FickCO2 , respectively) were compared with measurements from a flow probe placed on the aortic root. Independent of changes in measured oxygen delivery, cerebral and myocardial tPO2 increased in proportion to PaO2 , as did SvO2 (P<0.001 for all). Based on mixed model analysis, each 100mmHg increase in PaO2 resulted in a 4.8±0.9% increase in SvO2 under the conditions tested. Because neither measured oxygen consumption, arterial oxyhemoglobin saturation or cardiac output varied significantly during hyperoxia, changes in SvO2 resulted in successively increasing errors in FickO2 during hyperoxia (34% during normoxia, 72% during FiO2 0.8). FickCO2 lacked the progressively worsening errors present in FickO2 , but correlated poorly with CO. SvO2 acutely changes following changes in PaO2 even absent changes in measured DO2 . This may lead to errors in FickO2 estimates of CI. Further work is necessary to understand the impact of this phenomenon in disease states.

Biophysical basis of subthalamic local field potentials recorded from deep brain stimulation electrodes.

Clinical deep brain stimulation (DBS) technology is evolving to enable chronic recording of local field potentials (LFPs) that represent electrophysiological biomarkers of the underlying disease state. However, little is known about the biophysical basis of LFPs, or how the patient's unique brain anatomy and electrode placement impact the recordings. Therefore, we developed a patient-specific computational framework to analyze LFP recordings within a clinical DBS context. We selected a subject with Parkinson's disease implanted with a Medtronic Activa PC+S DBS system and reconstructed their subthalamic nucleus (STN) and DBS electrode location using medical imaging data. The patient-specific STN volume was populated with 235,280 multicompartment STN neuron models, providing a neuron density consistent with histological measurements. Each neuron received time-varying synaptic inputs and generated transmembrane currents that gave rise to the LFP signal recorded at DBS electrode contacts residing in a finite element volume conductor model. We then used the model to study the role of synchronous beta-band inputs to the STN neurons on the recorded power spectrum. Three bipolar pairs of simultaneous clinical LFP recordings were used in combination with an optimization algorithm to customize the neural activity parameters in the model to the patient. The optimized model predicted a 2.4-mm radius of beta-synchronous neurons located in the dorsolateral STN. These theoretical results enable biophysical dissection of the LFP signal at the cellular level with direct comparison to the clinical recordings, and the model system provides a scientific platform to help guide the design of DBS technology focused on the use of subthalamic beta activity in closed-loop algorithms. NEW & NOTEWORTHY The analysis of deep brain stimulation of local field potential (LFP) data is rapidly expanding from scientific curiosity to the basis for clinical biomarkers capable of improving the therapeutic efficacy of stimulation. With this growing clinical importance comes a growing need to understand the underlying electrophysiological fundamentals of the signals and the factors contributing to their modulation. Our model reconstructs the clinical LFP from first principles and highlights the importance of patient-specific factors in dictating the signals recorded.

Locomotion Control of Pigeons using Polymer-based Deep Brain Electrodes.

This paper describes the electrical modulation of locomotion in pigeons using deep brain electrodes. Polymer-based depth electrodes with four channels were fabricated. Based on the location of the nucleus intercollicularis (ICo), the shanks of the depth electrodes were designed to be a length of 11 mm. After the implantation of the depth electrode into the ICo region of the brain, it was connected by wires to a custom-made stimulator, and biphasic current pulses were delivered. Current pulses with an amplitude of 0.5 mA, a rate of 58.0 Hz, and a duration of $320\mu \mathrm{s} $s were applied for 0.5 s. When the ICo region was electrically stimulated, taking-off behavior was successfully induced for 0.4 s. Induction of taking-off behavior by electrical stimulation, when coupled to control of turning and running forward locomotions, may contribute to the development of remote flight-control system of freely moving pigeon.

Spectral and phase-amplitude coupling signatures in human deep brain oscillations during propofol-induced anaesthesia

BackgroundBoth the cerebral cortex and subcortical structures play important roles in consciousness. Some evidence points to general anaesthesia-induced unconsciousness being associated with distinct patterns of superficial cortical electrophysiological oscillations, but how general anaesthetics influence deep brain neural oscillations and interactions between oscillations in humans is poorly understood. MethodsLocal field potentials were recorded in discrete deep brain regions, including anterior cingulate cortex, sensory thalamus, and periaqueductal grey, in humans with implanted deep brain electrodes during induction of unconsciousness with propofol. Power-frequency spectra, phase-amplitude coupling, coherence, and directed functional connectivity analysis were used to characterise local field potentials in the awake and unconscious states. ResultsAn increase in alpha (7–13 Hz) power and decrease in gamma (30–90 Hz) power were observed in both deep cortical (ACC, anterior cingulate cortex) and subcortical (sensory thalamus, periaqueductal grey) areas during propofol-induced unconsciousness. Robust alpha-low gamma (30–60 Hz) phase-amplitude coupling induced by general anaesthesia was observed in the anterior cingulate cortex but not in other regions studied. Moreover, alpha oscillations during unconsciousness were highly coherent within the anterior cingulate cortex, and this rhythm exhibited a bidirectional information flow between left and right anterior cingulate cortex but stronger left-to-right flow. ConclusionPropofol increases alpha oscillations and attenuates gamma oscillations in both cortical and subcortical areas. The alpha-gamma phase-amplitude coupling and the functional connectivity of alpha oscillations in the anterior cingulate cortex could be specific markers for loss of consciousness.

A micro-CT-based method for quantitative brain lesion characterization and electrode localization

Lesion verification and quantification is traditionally done via histological examination of sectioned brains, a time-consuming process that relies heavily on manual estimation. Such methods are particularly problematic in posterior cortical regions (e.g. visual cortex), where sectioning leads to significant damage and distortion of tissue. Even more challenging is the post hoc localization of micro-electrodes, which relies on the same techniques, suffers from similar drawbacks and requires even higher precision. Here, we propose a new, simple method for quantitative lesion characterization and electrode localization that is less labor-intensive and yields more detailed results than conventional methods. We leverage staining techniques standard in electron microscopy with the use of commodity micro-CT imaging. We stain whole rat and zebra finch brains in osmium tetroxide, embed these in resin and scan entire brains in a micro-CT machine. The scans result in 3D reconstructions of the brains with section thickness dependent on sample size (12–15 and 5–6 microns for rat and zebra finch respectively) that can be segmented manually or automatically. Because the method captures the entire intact brain volume, comparisons within and across studies are more tractable, and the extent of lesions and electrodes may be studied with higher accuracy than with current methods.

Image Fusion of 3T and 1.5 T MRI for Parkinson’s Disease Surgery

Introduction. Anatomical landmarks for stereotactic surgical procedures like deep brain electrodes implantation for Parkinson’s Disease has been performed since a long time ago through low-field magnetic resonance image (MRI) such as 1.5 Tesla (T) apparatus. Methods: We describe a direct method of visualization of subthalamic nucleus. For this purpose, a routine 1.5T MRI images are taken, and undergoes further fusion with 3T MRI pictures. Results. The result of image fusion allows tridimensional reconstructions, and a better differentiation between white matter and gray matter of the brain. A higher resolution also gives better identification of subthalamic nucleus, skull base nucleus, red nucleus, as well as other anatomical landmarks, resulting in higher accuracy of the procedure. Conclusion. A computational platform combining these two MRIs (3T and 1.5T) has reached more accuracy for surgical implantation of electrodes in Deep Brain Stimulation for subthalamic nucleus.

Intracranial EEG fluctuates over months after implanting electrodes in human brain

Objective. Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings. Approach. Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for the duration of each patient’s recording. Metrics to capture post-implantation feature changes and inflexion points were computed on group and individual levels. A linear mixed model was used to characterize transient group-level changes in feature values post-implantation and independent linear models were used to describe individual variability. Main results. A significant decline in features important to seizure detection and prediction algorithms (mean line length, energy, and half-wave), as well as mean power in the Berger and high gamma bands, was observed in many patients over 100 d following implantation. In addition, spatial variability across electrodes declines post-implantation following a similar timeframe. All selected features decreased by 14–50% in the initial 75 d of recording on the group level, and at least one feature demonstrated this pattern in 13 of the 15 patients. Our findings indicate that iEEG signal features demonstrate increased variability following implantation, most notably in the weeks immediately post-implant. Significance. These findings suggest that conclusions drawn from iEEG, both clinically and for research, should account for spatiotemporal signal variability and that properly assessing the iEEG in patients, depending upon the application, may require extended monitoring.

S85 The modulatory role of subcortical structures on cortical cognitive functions

A direct way of studying the function of the subcortical nuclei is neurophysiological recording of event related electrical activities, i.e. the evoked potentials and oscillations, via the intracranial deep brain electrodes. Based on our own electrophysiological recordings and results of other groups we suggest that the subcortical nuclei are involved in the processing of higher cortical functions. We recorded cognitive tasks-related activities in putamen, pallidum, caudate, ncl. subthalamicus, anterior and posterolateral thalamus. Recordings were performed via intracerebral electrodes (SEEG) or deep brain stimulation (DBS) electrodes in patients with pharmacoresistant epilepsy from basal ganglia ( putamen, pallidum, caudate) and anterior nuclei of thalamus; in patients with Parkinson’s disease and dystonia from the subthalamic nucleus and internal pallidum; posterolateral thalamus was implanted for the treatment of pain. The cognitive role of the subcortical structures was tested in various protocols exploring the cognitive involvement in the motor control, executive functions, attention and orientation, complex visuo-motor tasks, memory encoding and retrieval. A general hypothesis explaining the role of the subcortical structures and the cortico-subcortical interactions in processing cognitive activities is still missing. We suggest that there is a plastic functional network of cortical and subcortical structures that are simultaneously active, with all the time changing mutual interconnections of active and inactive zones in a task related manner. 1. Basal ganglia – thalamocortical loop act as an modulator which may be involved in tuning the widespread cortical functions. An integrative role of the basal ganglia with subsequent modulation of cortical cognitive processing is suggested. 2. Thalamic specific nuclei may modulate specific cognitive functions probably via contextual modulation of certain cortical areas. Subcortical structures, in particular basal ganglia, should be seriously considered as a potential target for neuromodulatory treatment of diseases with cognitive disturbances.

Continuous Force Decoding from Deep Brain Local Field Potentials for Brain Computer Interfacing.

Current Brain Computer Interface (BCI) systems are limited by relying on neuronal spikes and decoding limited to kinematics only. For a BCI system to be practically useful, it should be able to decode brain information on a continuous basis with low latency. This study investigates if force can be decoded from local field potentials (LFP) recorded with deep brain electrodes located at the Subthalamic nucleus (STN) using data from 5 patients with Parkinson's disease, on a continuous basis with low latency. A Wiener-Cascade (WC) model based decoder was proposed using both time-domain and frequency-domain features. The results suggest that high gamma band (300-500Hz) activity, in addition to the beta (13-30Hz) and gamma band (55-90Hz) activity is the most informative for force prediction but combining all features led to better decoding performance. Furthermore, LFP signals preceding the force output by up to 1256 milliseconds were found to be predictive of the force output.

A tribute to Jose M.R. Delgado (1915–2011): The pioneer of electric brain-stimulation

IntroductionJosé Manuel Rodriguez Delgado (1915–2011), a Spanish physiologist, was among the first scientist to perform electric brain stimulation in both animals and humans. His work on brain-stimulation research during the 1960s and 1970s was innovative but also controversial.ObjectivesTo present the scientific papers of Jose Delgado on psychosurgery.AimsTo review available literature and to show evidence that Jose Delgado made a significant contribution to the development of psychosurgery.MethodsA biography and private papers are presented and discussed followed by a literature review.ResultsDelgado showed that with electrical brain stimulation one could evoke well-organized complex behavior in primates. A rhesus monkey was stimulated with an electrode implanted inside the red nucleus, followed by a complex sequence of events. After stimulation of an area three millimeters from the red nucleus, the rhesus monkey just yawned. Delgado also investigated the mechanisms of aggressive behavior in other animals. Stimulation of the caudate nucleus by remote control in a fighting bully resulted in sudden paralysis. In some human patients suffering from depression, euphoria was induced after stimulation of the septum.ConclusionDelgado pioneered the brain electrode implantation in order to electrically stimulate specific brain areas for treatment epilepsy and of different types of mental illness. He was severely criticized. His studies, however, paved the way for new modulation techniques such as the development of deep brain stimulation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The effects of gender and depression severity on the association between alpha asymmetry and depression across four brain regions

Data describing the association between EEG asymmetry and depression status have been equivocal. Effects from brain regions involved, depression severity, and the generalisability of findings across genders, have been inconsistently examined and/or verified. This study investigated these issues within a community sample to potentially expand the asymmetry hypothesis to non-severe depression participants. The singular effects of brain region and electrode site, gender, and depression severity, plus the interaction between gender and depression severity across brain regions were investigated in a study of alpha asymmetry among 46 males and 54 females (M age=32.5 yr, SD=14.13 yr) using the Self-rating Depression Scale (Zung, 1973). There was no significant difference across genders or age for depression severity. Dichotomous classification of depressed state produced similar but slightly different results from analysis of the whole range of depression status, although the frontal region was the only area where depression was consistently significantly associated with EEG asymmetry, and then only for females. However, the direction of those differences for females was opposite of that predicted by the EEG asymmetry-depression hypothesis. Several methodological issues that may have contributed to these findings are discussed, with suggestions made for future research that focusses upon individual depression symptom profiles rather than dichotomous or total depression scores in order to assist in developing a clinically-relevant model of EEG asymmetry in depressed persons.

Decoding force from deep brain electrodes in Parkinsonian patients.

Limitations of many Brain Machine Interface (BMI) systems using invasive electrodes include reliance on single neurons and decoding limited to kinematics only. This study investigates whether force-related information is present in the local field potential (LFP) recorded with deep brain electrodes using data from 14 patients with Parkinson's disease. A classifier based on logistic regression (LR) is developed to classify various force stages, using 10-fold cross validation. Least Absolute and Shrinkage Operator (Lasso) is then employed in order to identify the features with the most predictivity. The results show that force-related information is present in the LFP, and it is possible to distinguish between various force stages using certain frequency-domain (delta, beta, gamma) and time-domain (mobility) features in real-time.

Novel semi-dry electrodes for brain–computer interface applications

Objectives. Modern applications of brain–computer interfaces (BCIs) based on electroencephalography rely heavily on the so-called wet electrodes (e.g. Ag/AgCl electrodes) which require gel application and skin preparation to operate properly. Recently, alternative ‘dry’ electrodes have been developed to increase ease of use, but they often suffer from higher electrode–skin impedance and signal instability. In the current paper, we have proposed a novel porous ceramic-based ‘semi-dry’ electrode. The key feature of the semi-dry electrodes is that their tips can slowly and continuously release a tiny amount of electrolyte liquid to the scalp, which provides an ionic conducting path for detecting neural signals. Approach. The performance of the proposed electrode was evaluated by simultaneous recording of the wet and semi-dry electrodes pairs in five classical BCI paradigms: eyes open/closed, the motor imagery BCI, the P300 speller, the N200 speller and the steady-state visually evoked potential-based BCI. Main results. The grand-averaged temporal cross-correlation was 0.95 ± 0.07 across the subjects and the nine recording positions, and these cross-correlations were stable throughout the whole experimental protocol. In the spectral domain, the semi-dry/wet coherence was greater than 0.80 at all frequencies and greater than 0.90 at frequencies above 10 Hz, with the exception of a dip around 50 Hz (i.e. the powerline noise). More importantly, the BCI classification accuracies were also comparable between the two types of electrodes. Significance. Overall, these results indicate that the proposed semi-dry electrode can effectively capture the electrophysiological responses and is a feasible alternative to the conventional dry electrode in BCI applications.

Stereo-electro-encephalography−Guided Radiofrequency Thermocoagulation: From In Vitro and In Vivo Data to Technical Guidelines

Deep brain electrodes have been used for the past 10 years to produce bipolar stereo-electro-encephalography-guided radiofrequency thermocoagulation (SEEG RF-TC). However, this technique is based on empiric knowledge. The aim of this study is 3-fold: 1) provide invivo animal data concerning the effect of bipolar RF-TC on brain and its safety; 2) assess the parameters of this procedure (current delivery and dipole selection) that produce the most efficient lesion; and 3) provide technical guidelines. First we achieved invivo RF-TC on rabbit brains with several conditions (power delivered and lesioning duration) and analyzed their influence on the lesion produced. Only a difference in terms of volume was found, and type of histologic lesions was similar whatever the settings were. We then performed multiple RF-TC invitro on egg albumen, first with several parameters of radiofrequency and then with different dipole spatial selections. The end point was the size of the radiofrequency thermolesion produced. Using unfixed parameters of radiofrequency current delivery and increasing it until the power delivered by the generator collapsed produced significantly larger lesions (P= 0.008) than other conditions. Concerning the dipole selection, the use of contiguous contacts on electrodes led to lesions with a higher volume (P= 7.7× 10-13) than those produced with noncontiguous ones. Besides the target selection in SEEG RF-TC, which is summarized on the basis of a literature review, we report the optimal parameters: Radiofrequency current must be increased until the power delivered collapses, and dipoles should be constituted by contiguous electrode contacts.

Hyperkinetic disorders and loss of synaptic downscaling.

Recent clinical and preclinical studies have shown that hyperkinetic disorders such as Huntington's disease, dystonia and l-DOPA-induced dyskinesia in Parkinson's disease are all characterized by loss of the ability to reverse synaptic plasticity and an associated increase in the excitability of excitatory neuronal inputs to a range of cortical and subcortical brain areas. Moreover, these changes have been detected in humans with hyperkinetic disorders either via direct recordings from implanted deep brain electrodes or noninvasively using transcranial magnetic stimulation. Here we discuss the mechanisms underlying the loss of bidirectional plasticity and the possibility that future interventions could be devised to reverse these changes in patients with hyperkinetic movement disorders.

Stereoelectroencephalography by using O-Arm® and Vertek® passive articulated arm: Technical note and experience of an epilepsy referral centre

To report a novel, accurate, and safe technique for deep brain electrode implantation to register brain electrical activity or SEEG, using frameless stereotaxy, neuronavigation assisted, and intraoperative CT-guided O-Arm® and the Vertek® articulated passive arm. All patients implanted by this technique in Barcelona Hospital Clinic were included. A prospective evaluation was made of the accuracy of the technique, as well as complications, surgical time, length of stay, and short-term outcomes. The study included 10 patients that underwent this procedure. The mean age was 38 years, and 60% were women. A mean of 6.9 (3-10) electrodes/patient, with a total of 69 electrodes, were implanted. The mean time for implantation was 34.7minutes per electrode. The mean distance between the planned target and the final target was 1.39 millimetres (0.95-1.7). There were no surgically derived complications. The epileptogenic zone was determined in 6 cases (60%). Surgical resection was performed in 5 cases (50%), with thermocoagulation in 3 (30%) cases, and in 2 cases (20%) there was no treatment. At a six-month follow-up of the 8 treated cases, 37.5% were ELAI I, 12.5% ELAI III, 25% ELAI IV, and 25% ELAI V. The implantation of deep brain electrodes for SEEG by using intraoperative CT O-Arm® and the Vertek® articulated passive arm is a safe and effective technique with adequate accuracy.

Attenuation of pathological spectral theta power by deep brain stimulation in a Parkinson patient

A patient (born in 1943) with generalized anxiety since 2008 developed Parkinsonian tremor in 2010. First quantitative EEG recording (neo-CATEEM software using 10/20 electrode positions) was obtained on 10.02.2011. Comparison of spectral power to a norm database of 500 healthy brains revealed enhanced theta power (5–7 Hz) at temporal electrode positions T5 and T6 with a statistical probability of 10000 to 1. This feature was seen under both recording conditions “eyes open” and “eyes closed”. In 11/2012 he got two deep brain electrodes implanted into the nucleus subthalamicus. EEG findings as seen before were reproduced on 22.02.2013 and 24.09.2013. In order to measure the effectiveness of the stimulation further recordings were taken without active stimulation and in the presence of active stimulation on 28.07.2014 and 24.09.2014. During stimulation spectral theta power was attenuated by 50% in comparison to the pre-stimulation recording only at electrode position T6 at both timings (videoclip). The results not only confirm the view that temporal spectral theta power seems to reflect movement problems like tremor but also signalizes that this pathological feature can be influenced successfully by deep brain stimulation. Quantitative EEG recordings might provide a reasonable control for deep brain stimulation in general.

Insights into affective word processing and geriatric depression through the combination of Event-Related Potentials with Cortical Brain Network Analysis

Insights into affective word processing and geriatric depression through the combination of Event-Related Potentials with Cortical Brain Network Analysis

Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time.

OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional stereotactic procedures.

Learning from brain control: clinical application of brain–computer interfaces

Abstract Brain-computer interfaces (BCI) use neuroelectric and metabolic brain activity to activate peripheral devices and computers without mediation of the motor system. In order to activate the BCI patients have to learn a certain amount of brain control. Self-regulation of brain activity was found to follow the principles of skill learning and instrumental conditioning. This review focuses on the clinical application of brain-computer interfaces in paralyzed patients with locked-in syndrome and completely locked-in syndrome (CLIS). It was shown that electroencephalogram (EEG)-based brain-computer interfaces allow selection of letters and words in a computer menu with different types of EEG signals. However, in patients with CLIS without any muscular control, particularly of eye movements, classical EEG-based brain-computer interfaces were not successful. Even after implantation of electrodes in the human brain, CLIS patients were unable to communicate. We developed a theoretical model explaining this fundamental deficit in instrumental learning of brain control and voluntary communication: patients in complete paralysis extinguish goal-directed responseoriented thinking and intentions. Therefore, a reflexive classical conditioning procedure was developed and metabolic brain signals measured with near infrared spectroscopy were used in CLIS patients to answer simple questions with a “yes” or “no”-brain response. The data collected so far are promising and show that for the first time CLIS patients communicate with such a BCI system using metabolic brain signals and simple reflexive learning tasks. Finally, brain machine interfaces and rehabilitation in chronic stroke are described demonstrating in chronic stroke patients without any residual upper limb movement a surprising recovery of motor function on the motor level as well as on the brain level. After extensive combined BCI training with behaviorally oriented physiotherapy, significant improvement in motor function was shown in this previously intractable paralysis. In conclusion, clinical application of brain machine interfaces in well-defined and circumscribed neurological disorders have demonstrated surprisingly positive effects. The application of BCIs to psychiatric and clinical-psychological problems, however, at present did not result in substantial improvement of complex behavioral disorders.