Passive functional mapping of receptive language areas using electrocorticographic signals.

OBJECTIVE: To validate the use of passive functional mapping using electrocorticographic (ECoG) broadband gamma signals for identifying receptive language cortex. METHODS: We mapped language function in 23 patients using ECoG and using electrical cortical stimulation (ECS) in a subset of 15 subjects. RESULTS: The qualitative comparison between cortical sites identified by ECoG and ECS show a high concordance. A quantitative comparison indicates a high level of sensitivity (95%) and a lower level of specificity (59%). Detailed analysis reveals that 82% of all cortical sites identified by ECoG were within one contact of a site identified by ECS. CONCLUSIONS: These results show that passive functional mapping reliably localizes receptive language areas, and that there is a substantial concordance between the ECoG- and ECS-based methods. They also point to a more refined understanding of the differences between ECoG- and ECS-based mappings. This refined understanding helps to clarify the instances in which the two methods disagree and can explain why neurosurgical practice has established the concept of a "safety margin." SIGNIFICANCE: Passive functional mapping using ECoG signals provides a fast, robust, and reliable method for identifying receptive language areas without many of the risks and limitations associated with ECS.

Real-time detection and discrimination of visual perception using electrocorticographic signals.

OBJECTIVE: Several neuroimaging studies have demonstrated that the ventral temporal cortex contains specialized regions that process visual stimuli. This study investigated the spatial and temporal dynamics of electrocorticographic (ECoG) responses to different types and colors of visual stimulation that were presented to four human participants, and demonstrated a real-time decoder that detects and discriminates responses to untrained natural images. APPROACH: ECoG signals from the participants were recorded while they were shown colored and greyscale versions of seven types of visual stimuli (images of faces, objects, bodies, line drawings, digits, and kanji and hiragana characters), resulting in 14 classes for discrimination (experiment I). Additionally, a real-time system asynchronously classified ECoG responses to faces, kanji and black screens presented via a monitor (experiment II), or to natural scenes (i.e. the face of an experimenter, natural images of faces and kanji, and a mirror) (experiment III). Outcome measures in all experiments included the discrimination performance across types based on broadband γ activity. MAIN RESULTS: Experiment I demonstrated an offline classification accuracy of 72.9% when discriminating among the seven types (without color separation). Further discrimination of grey versus colored images reached an accuracy of 67.1%. Discriminating all colors and types (14 classes) yielded an accuracy of 52.1%. In experiment II and III, the real-time decoder correctly detected 73.7% responses to face, kanji and black computer stimuli and 74.8% responses to presented natural scenes. SIGNIFICANCE: Seven different types and their color information (either grey or color) could be detected and discriminated using broadband γ activity. Discrimination performance maximized for combined spatial-temporal information. The discrimination of stimulus color information provided the first ECoG-based evidence for color-related population-level cortical broadband γ responses in humans. Stimulus categories can be detected by their ECoG responses in real time within 500 ms with respect to stimulus onset.

Monitoring of complement activation biomarkers and eculizumab in complement-mediated renal disorders.

Various complement-mediated renal disorders are treated currently with the complement inhibitor eculizumab. By blocking the cleavage of C5, this monoclonal antibody prevents cell damage caused by complement-mediated inflammation. We included 23 patients with atypical haemolytic uraemic syndrome (aHUS, n = 12), C3 glomerulopathies (C3G, n = 9) and acute antibody-mediated renal graft rejection (AMR, n = 2), treated with eculizumab in 12 hospitals in Germany. We explored the course of complement activation biomarkers and the benefit of therapeutic drug monitoring of eculizumab. Complement activation was assessed by analysing the haemolytic complement function of the classical (CH50) and the alternative pathway (APH50), C3 and the activation products C3d, C5a and sC5b-9 prior to, 3 and 6 months after eculizumab treatment. Eculizumab concentrations were determined by a newly established specific enzyme-linked immunosorbent assay (ELISA). Serum eculizumab concentrations up to 1082 µg/ml point to drug accumulation, especially in paediatric patients. Loss of the therapeutic antibody via urine with concentrations up to 56 µg/ml correlated with proteinuria. In aHUS patients, effective complement inhibition was demonstrated by significant reductions of CH50, APH50, C3d and sC5b-9 levels, whereas C5a levels were only reduced significantly after 6 months' treatment. C3G patients presented increased C3d and consistently low C3 levels, reflecting ongoing complement activation and consumption at the C3 level, despite eculizumab treatment. A comprehensive complement analysis together with drug monitoring is required to distinguish mode of complement activation and efficacy of eculizumab treatment in distinct renal disorders. Accumulation of the anti-C5 antibody points to the need for a patient-orientated tailored therapy.

A method to establish the spatiotemporal evolution of task-related cortical activity from electrocorticographic signals in single trials.

BACKGROUND: Progress in neuroscience depends substantially on the ability to establish the detailed spatial and temporal sequence of neuronal population-level activity across large areas of the brain. Because there is substantial inter-trial variability in neuronal activity, traditional techniques that rely on signal averaging obscure where and when neuronal activity occurs. Thus, up to the present, it has been difficult to examine the detailed progression of neuronal activity across large areas of the brain. NEW METHOD: Here we describe a method for establishing the spatiotemporal evolution of neuronal population-level activity across large brain regions by determining exactly where and when neural activity occurs during a behavioral task in individual trials. We validate the efficacy of the method, examine the effects of its parameterization, and demonstrate its utility by highlighting two sets of results that could not readily be achieved with traditional methods. RESULTS: Our results reveal the precise spatiotemporal evolution of neuronal population activity that unfolds during a sensorimotor task in individual trials, and establishes the relationship between neuronal oscillations and the onset of this activity. CONCLUSIONS: The ability to identify the spatiotemporal evolution of neuronal population activity onsets in single trials gives investigators a powerful new tool with which to study large-scale cortical processes.

Alpha power indexes task-related networks on large and small scales: A multimodal ECoG study in humans and a non-human primate.

Performing different tasks, such as generating motor movements or processing sensory input, requires the recruitment of specific networks of neuronal populations. Previous studies suggested that power variations in the alpha band (8-12Hz) may implement such recruitment of task-specific populations by increasing cortical excitability in task-related areas while inhibiting population-level cortical activity in task-unrelated areas (Klimesch et al., 2007; Jensen and Mazaheri, 2010). However, the precise temporal and spatial relationships between the modulatory function implemented by alpha oscillations and population-level cortical activity remained undefined. Furthermore, while several studies suggested that alpha power indexes task-related populations across large and spatially separated cortical areas, it was largely unclear whether alpha power also differentially indexes smaller networks of task-related neuronal populations. Here we addressed these questions by investigating the temporal and spatial relationships of electrocorticographic (ECoG) power modulations in the alpha band and in the broadband gamma range (70-170Hz, indexing population-level activity) during auditory and motor tasks in five human subjects and one macaque monkey. In line with previous research, our results confirm that broadband gamma power accurately tracks task-related behavior and that alpha power decreases in task-related areas. More importantly, they demonstrate that alpha power suppression lags population-level activity in auditory areas during the auditory task, but precedes it in motor areas during the motor task. This suppression of alpha power in task-related areas was accompanied by an increase in areas not related to the task. In addition, we show for the first time that these differential modulations of alpha power could be observed not only across widely distributed systems (e.g., motor vs. auditory system), but also within the auditory system. Specifically, alpha power was suppressed in the locations within the auditory system that most robustly responded to particular sound stimuli. Altogether, our results provide experimental evidence for a mechanism that preferentially recruits task-related neuronal populations by increasing cortical excitability in task-related cortical areas and decreasing cortical excitability in task-unrelated areas. This mechanism is implemented by variations in alpha power and is common to humans and the non-human primate under study. These results contribute to an increasingly refined understanding of the mechanisms underlying the selection of the specific neuronal populations required for task execution.

Oscillatory phase modulates the timing of neuronal activations and resulting behavior.

Human behavioral response timing is highly variable from trial to trial. While it is generally understood that behavioral variability must be due to trial-by-trial variations in brain function, it is still largely unknown which physiological mechanisms govern the timing of neural activity as it travels through networks of neuronal populations, and how variations in the timing of neural activity relate to variations in the timing of behavior. In our study, we submitted recordings from the cortical surface to novel analytic techniques to chart the trajectory of neuronal population activity across the human cortex in single trials, and found joint modulation of the timing of this activity and of consequent behavior by neuronal oscillations in the alpha band (8-12Hz). Specifically, we established that the onset of population activity tends to occur during the trough of oscillatory activity, and that deviations from this preferred relationship are related to changes in the timing of population activity and the speed of the resulting behavioral response. These results indicate that neuronal activity incurs variable delays as it propagates across neuronal populations, and that the duration of each delay is a function of the instantaneous phase of oscillatory activity. We conclude that the results presented in this paper are supportive of a general model for variability in the effective speed of information transmission in the human brain and for variability in the timing of human behavior.

The effects of spatial filtering and artifacts on electrocorticographic signals.

OBJECTIVE: Electrocorticographic (ECoG) signals contain noise that is common to all channels and noise that is specific to individual channels. Most published ECoG studies use common average reference (CAR) spatial filters to remove common noise, but CAR filters may introduce channel-specific noise into other channels. To address this concern, scientists often remove artifactual channels prior to data analysis. However, removing these channels depends on expert-based labeling and may also discard useful data. Thus, the effects of spatial filtering and artifacts on ECoG signals have been largely unknown. This study aims to quantify these effects and thereby address this gap in knowledge. APPROACH: In this study, we address these issues by exploring the effects of application of two types of unsupervised spatial filters and three methods of detecting signal artifacts using a large ECoG data set (20 subjects, four task conditions in each subject). MAIN RESULTS: Our results confirm that spatial filtering improves performance, i.e., it reduces ECoG signal variance that is not related to the task. They also show that removing artifactual channels automatically (using quantitatively defined rejection criteria) or manually (using expert opinion) does not increase the total amount of task-related information, but does avoid potential contamination from one or more noisy channels. Finally, applying a novel 'median average reference' filter does not require the elimination of artifactual channels prior to spatial filtering and still mitigates the influence of channels with channel-specific noise. Thus, it allows the investigator to retain more potentially useful task-related data. SIGNIFICANCE: In summary, our results show that appropriately designed spatial filters that account for both common noise and channel-specific noise greatly improve the quality of ECoG signal analyses, and that artifacts in only a single channel can result in profound and undesired effects on all other channels.

Identifying the Attended Speaker Using Electrocorticographic (ECoG) Signals.

People affected by severe neuro-degenerative diseases (e.g., late-stage amyotrophic lateral sclerosis (ALS) or locked-in syndrome) eventually lose all muscular control. Thus, they cannot use traditional assistive communication devices that depend on muscle control, or brain-computer interfaces (BCIs) that depend on the ability to control gaze. While auditory and tactile BCIs can provide communication to such individuals, their use typically entails an artificial mapping between the stimulus and the communication intent. This makes these BCIs difficult to learn and use. In this study, we investigated the use of selective auditory attention to natural speech as an avenue for BCI communication. In this approach, the user communicates by directing his/her attention to one of two simultaneously presented speakers. We used electrocorticographic (ECoG) signals in the gamma band (70-170 Hz) to infer the identity of attended speaker, thereby removing the need to learn such an artificial mapping. Our results from twelve human subjects show that a single cortical location over superior temporal gyrus or pre-motor cortex is typically sufficient to identify the attended speaker within 10 s and with 77% accuracy (50% accuracy due to chance). These results lay the groundwork for future studies that may determine the real-time performance of BCIs based on selective auditory attention to speech.

Current trends in hardware and software for brain-computer interfaces (BCIs).

A brain-computer interface (BCI) provides a non-muscular communication channel to people with and without disabilities. BCI devices consist of hardware and software. BCI hardware records signals from the brain, either invasively or non-invasively, using a series of device components. BCI software then translates these signals into device output commands and provides feedback. One may categorize different types of BCI applications into the following four categories: basic research, clinical/translational research, consumer products, and emerging applications. These four categories use BCI hardware and software, but have different sets of requirements. For example, while basic research needs to explore a wide range of system configurations, and thus requires a wide range of hardware and software capabilities, applications in the other three categories may be designed for relatively narrow purposes and thus may only need a very limited subset of capabilities. This paper summarizes technical aspects for each of these four categories of BCI applications. The results indicate that BCI technology is in transition from isolated demonstrations to systematic research and commercial development. This process requires several multidisciplinary efforts, including the development of better integrated and more robust BCI hardware and software, the definition of standardized interfaces, and the development of certification, dissemination and reimbursement procedures.

Does the 'P300' speller depend on eye gaze?

Many people affected by debilitating neuromuscular disorders such as amyotrophic lateral sclerosis, brainstem stroke or spinal cord injury are impaired in their ability to, or are even unable to, communicate. A brain-computer interface (BCI) uses brain signals, rather than muscles, to re-establish communication with the outside world. One particular BCI approach is the so-called 'P300 matrix speller' that was first described by Farwell and Donchin (1988 Electroencephalogr. Clin. Neurophysiol. 70 510-23). It has been widely assumed that this method does not depend on the ability to focus on the desired character, because it was thought that it relies primarily on the P300-evoked potential and minimally, if at all, on other EEG features such as the visual-evoked potential (VEP). This issue is highly relevant for the clinical application of this BCI method, because eye movements may be impaired or lost in the relevant user population. This study investigated the extent to which the performance in a 'P300' speller BCI depends on eye gaze. We evaluated the performance of 17 healthy subjects using a 'P300' matrix speller under two conditions. Under one condition ('letter'), the subjects focused their eye gaze on the intended letter, while under the second condition ('center'), the subjects focused their eye gaze on a fixation cross that was located in the center of the matrix. The results show that the performance of the 'P300' matrix speller in normal subjects depends in considerable measure on gaze direction. They thereby disprove a widespread assumption in BCI research, and suggest that this BCI might function more effectively for people who retain some eye-movement control. The applicability of these findings to people with severe neuromuscular disabilities (particularly in eye-movements) remains to be determined.

Decoding flexion of individual fingers using electrocorticographic signals in humans.

Brain signals can provide the basis for a non-muscular communication and control system, a brain-computer interface (BCI), for people with motor disabilities. A common approach to creating BCI devices is to decode kinematic parameters of movements using signals recorded by intracortical microelectrodes. Recent studies have shown that kinematic parameters of hand movements can also be accurately decoded from signals recorded by electrodes placed on the surface of the brain (electrocorticography (ECoG)). In the present study, we extend these results by demonstrating that it is also possible to decode the time course of the flexion of individual fingers using ECoG signals in humans, and by showing that these flexion time courses are highly specific to the moving finger. These results provide additional support for the hypothesis that ECoG could be the basis for powerful clinically practical BCI systems, and also indicate that ECoG is useful for studying cortical dynamics related to motor function.

Two-dimensional movement control using electrocorticographic signals in humans.

We show here that a brain-computer interface (BCI) using electrocorticographic activity (ECoG) and imagined or overt motor tasks enables humans to control a computer cursor in two dimensions. Over a brief training period of 12-36 min, each of five human subjects acquired substantial control of particular ECoG features recorded from several locations over the same hemisphere, and achieved average success rates of 53-73% in a two-dimensional four-target center-out task in which chance accuracy was 25%. Our results support the expectation that ECoG-based BCIs can combine high performance with technical and clinical practicality, and also indicate promising directions for further research.

Brain-computer interfaces (BCIs): detection instead of classification.

Many studies over the past two decades have shown that people can use brain signals to convey their intent to a computer through brain-computer interfaces (BCIs). These devices operate by recording signals from the brain and translating these signals into device commands. They can be used by people who are severely paralyzed to communicate without any use of muscle activity. One of the major impediments in translating this novel technology into clinical applications is the current requirement for preliminary analyses to identify the brain signal features best suited for communication. This paper introduces and validates signal detection, which does not require such analysis procedures, as a new concept in BCI signal processing. This detection concept is realized with Gaussian mixture models (GMMs) that are used to model resting brain activity so that any change in relevant brain signals can be detected. It is implemented in a package called SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection). The results indicate that SIGFRIED produces results that are within the range of those achieved using a common analysis strategy that requires preliminary identification of signal features. They indicate that such laborious analysis procedures could be replaced by merely recording brain signals during rest. In summary, this paper demonstrates how SIGFRIED could be used to overcome one of the present impediments to translation of laboratory BCI demonstrations into clinically practical applications.

Decoding two-dimensional movement trajectories using electrocorticographic signals in humans.

Signals from the brain could provide a non-muscular communication and control system, a brain-computer interface (BCI), for people who are severely paralyzed. A common BCI research strategy begins by decoding kinematic parameters from brain signals recorded during actual arm movement. It has been assumed that these parameters can be derived accurately only from signals recorded by intracortical microelectrodes, but the long-term stability of such electrodes is uncertain. The present study disproves this widespread assumption by showing in humans that kinematic parameters can also be decoded from signals recorded by subdural electrodes on the cortical surface (ECoG) with an accuracy comparable to that achieved in monkey studies using intracortical microelectrodes. A new ECoG feature labeled the local motor potential (LMP) provided the most information about movement. Furthermore, features displayed cosine tuning that has previously been described only for signals recorded within the brain. These results suggest that ECoG could be a more stable and less invasive alternative to intracortical electrodes for BCI systems, and could also prove useful in studies of motor function.

Patients with ALS can use sensorimotor rhythms to operate a brain-computer interface.

People with severe motor disabilities can maintain an acceptable quality of life if they can communicate. Brain-computer interfaces (BCIs), which do not depend on muscle control, can provide communication. Four people severely disabled by ALS learned to operate a BCI with EEG rhythms recorded over sensorimotor cortex. These results suggest that a sensorimotor rhythm-based BCI could help maintain quality of life for people with ALS.

EEG-based communication: presence of an error potential.

BACKGROUND: EEG-based communication could be a valuable new augmentative communication technology for those with severe motor disabilities. Like all communication methods, it faces the problem of errors in transmission. In the Wadsworth EEG-based brain-computer interface (BCI) system, subjects learn to use mu or beta rhythm amplitude to move a cursor to targets on a computer screen. While cursor movement is highly accurate in trained subjects, it is not perfect. METHODS: In an effort to develop a method for detecting errors, this study compared the EEG immediately after correct target selection to that after incorrect selection. RESULTS: The data showed that a mistake is followed by a positive potential centered at the vertex that peaks about 180 ms after the incorrect selection. CONCLUSION: The results suggest that this error potential might provide a method for detecting and voiding errors that requires no additional time and could thereby improve the speed and accuracy of EEG-based communication.

Brain-computer interface technology: a review of the first international meeting.

Over the past decade, many laboratories have begun to explore brain-computer interface (BCI) technology as a radically new communication option for those with neuromuscular impairments that prevent them from using conventional augmentative communication methods. BCI's provide these users with communication channels that do not depend on peripheral nerves and muscles. This article summarizes the first international meeting devoted to BCI research and development. Current BCI's use electroencephalographic (EEG) activity recorded at the scalp or single-unit activity recorded from within cortex to control cursor movement, select letters or icons, or operate a neuroprosthesis. The central element in each BCI is a translation algorithm that converts electrophysiological input from the user into output that controls external devices. BCI operation depends on effective interaction between two adaptive controllers, the user who encodes his or her commands in the electrophysiological input provided to the BCI, and the BCI which recognizes the commands contained in the input and expresses them in device control. Current BCI's have maximum information transfer rates of 5-25 b/min. Achievement of greater speed and accuracy depends on improvements in signal processing, translation algorithms, and user training. These improvements depend on increased interdisciplinary cooperation between neuroscientists, engineers, computer programmers, psychologists, and rehabilitation specialists, and on adoption and widespread application of objective methods for evaluating alternative methods. The practical use of BCI technology depends on the development of appropriate applications, identification of appropriate user groups, and careful attention to the needs and desires of individual users. BCI research and development will also benefit from greater emphasis on peer-reviewed publications, and from adoption of standard venues for presentations and discussion.