Applicability and robustness of the hen's egg test for analysis of micronucleus induction (HET-MN): results from an inter-laboratory trial.

The hen's egg test for analysis of micronucleus formation (HET-MN) was developed several years ago to provide an alternative test system to the in vivo micronucleus test. In order to assess its applicability and robustness, a study was carried out at the University of Osnabrueck (lab A) and at the laboratories of Henkel AG & Co. KGaA (lab B). Following transfer of the method to lab B, a range of test substances that had been pre-tested at lab A, were tested at Henkel: the genotoxins cyclophosphamide, dimethylbenz(a)anthracene, methotrexate, acrylamide, azorubin, N-nitroso-dimethylamine and the non-genotoxins, orange G and isopropyl myristate. In a second phase, additional compounds with known in vivo properties were examined in both labs: the non-genotoxin, ampicillin, the "irrelevant" positives, isophorone and 2,4-dichlorophenol ("irrelevant" means positive in standard in vitro tests, but negative in vivo), the clastogen p-chloroaniline, and the aneugens carbendazim and vinorelbine. All substances were correctly predicted in both labs with respect to their in vivo genotoxic properties, indicating that the HET-MN may have an improved predictivity compared with current standard in vitro test systems. The results support the promising role of the HET-MN assay as a supplement to existing test batteries.

Feasibility study to support a threshold of sensitization concern concept in risk assessment based on human data.

In analogy to the Threshold of Toxicological Concern concept, a Threshold of Sensitization Concern (TSC) concept is proposed for chemicals with respect to their ability to induce an allergic contact dermatitis. Recently, the derivation of a dermal sensitization threshold was suggested based on an evaluation of animal data. In order to establish the concept with human data, we conducted a meta-analysis taking into account No Expected Sensitization Induction Levels for fragrance ingredients from the IFRA/RIFM dataset. Based on a statistical analysis by applying Sensitization Assessment Factors that account for interindividual variability and different exposure conditions, TSC values of 0.91 or 0.30 lg/cm2 can be derived in terms of amount per skin area. TSC values are compared with typical exposure levels of cosmetic products. A substance can be considered to be virtually safe if the quotient of exposure level and TSC is < 1. The findings derived from human data include several conservative assumptions and largely support the dermal sensitization thresholds previously derived from animal data. The TSC concept might in principle be used for any untested chemical and therefore help in some cases to waive animal testing.

The Berlin Brain--Computer Interface: accurate performance from first-session in BCI-naïve subjects.

The Berlin Brain--Computer Interface (BBCI) project develops a noninvasive BCI system whose key features are: 1) the use of well-established motor competences as control paradigms; 2) high-dimensional features from multichannel EEG; and 3) advanced machine-learning techniques. Spatio-spectral changes of sensorimotor rhythms are used to discriminate imagined movements (left hand, right hand, and foot). A previous feedback study [M. Krauledat, K.-R. MUller, and G. Curio. (2007) The non-invasive Berlin brain--computer Interface: Fast acquisition of effective performance in untrained subjects. NeuroImage. [Online]. 37(2), pp. 539--550. Available: http://dx.doi.org/10.1016/j.neuroimage.2007.01.051] with ten subjects provided preliminary evidence that the BBCI system can be operated at high accuracy for subjects with less than five prior BCI exposures. Here, we demonstrate in a group of 14 fully BCI-naIve subjects that 8 out of 14 BCI novices can perform at >84% accuracy in their very first BCI session, and a further four subjects at >70%. Thus, 12 out of 14 BCI-novices had significant above-chance level performances without any subject training even in the first session, as based on an optimized EEG analysis by advanced machine-learning algorithms.

Towards zero training for brain-computer interfacing.

Electroencephalogram (EEG) signals are highly subject-specific and vary considerably even between recording sessions of the same user within the same experimental paradigm. This challenges a stable operation of Brain-Computer Interface (BCI) systems. The classical approach is to train users by neurofeedback to produce fixed stereotypical patterns of brain activity. In the machine learning approach, a widely adapted method for dealing with those variances is to record a so called calibration measurement on the beginning of each session in order to optimize spatial filters and classifiers specifically for each subject and each day. This adaptation of the system to the individual brain signature of each user relieves from the need of extensive user training. In this paper we suggest a new method that overcomes the requirement of these time-consuming calibration recordings for long-term BCI users. The method takes advantage of knowledge collected in previous sessions: By a novel technique, prototypical spatial filters are determined which have better generalization properties compared to single-session filters. In particular, they can be used in follow-up sessions without the need to recalibrate the system. This way the calibration periods can be dramatically shortened or even completely omitted for these 'experienced' BCI users. The feasibility of our novel approach is demonstrated with a series of online BCI experiments. Although performed without any calibration measurement at all, no loss of classification performance was observed.

Machine learning for real-time single-trial EEG-analysis: from brain-computer interfacing to mental state monitoring.

Machine learning methods are an excellent choice for compensating the high variability in EEG when analyzing single-trial data in real-time. This paper briefly reviews preprocessing and classification techniques for efficient EEG-based brain-computer interfacing (BCI) and mental state monitoring applications. More specifically, this paper gives an outline of the Berlin brain-computer interface (BBCI), which can be operated with minimal subject training. Also, spelling with the novel BBCI-based Hex-o-Spell text entry system, which gains communication speeds of 6-8 letters per minute, is discussed. Finally the results of a real-time arousal monitoring experiment are presented.

The non-invasive Berlin Brain-Computer Interface: fast acquisition of effective performance in untrained subjects.

Brain-Computer Interface (BCI) systems establish a direct communication channel from the brain to an output device. These systems use brain signals recorded from the scalp, the surface of the cortex, or from inside the brain to enable users to control a variety of applications. BCI systems that bypass conventional motor output pathways of nerves and muscles can provide novel control options for paralyzed patients. One classical approach to establish EEG-based control is to set up a system that is controlled by a specific EEG feature which is known to be susceptible to conditioning and to let the subjects learn the voluntary control of that feature. In contrast, the Berlin Brain-Computer Interface (BBCI) uses well established motor competencies of its users and a machine learning approach to extract subject-specific patterns from high-dimensional features optimized for detecting the user's intent. Thus the long subject training is replaced by a short calibration measurement (20 min) and machine learning (1 min). We report results from a study in which 10 subjects, who had no or little experience with BCI feedback, controlled computer applications by voluntary imagination of limb movements: these intentions led to modulations of spontaneous brain activity specifically, somatotopically matched sensorimotor 7-30 Hz rhythms were diminished over pericentral cortices. The peak information transfer rate was above 35 bits per minute (bpm) for 3 subjects, above 23 bpm for two, and above 12 bpm for 3 subjects, while one subject could achieve no BCI control. Compared to other BCI systems which need longer subject training to achieve comparable results, we propose that the key to quick efficiency in the BBCI system is its flexibility due to complex but physiologically meaningful features and its adaptivity which respects the enormous inter-subject variability.

Combined optimization of spatial and temporal filters for improving brain-computer interfacing.

Brain-computer interface (BCI) systems create a novel communication channel from the brain to an output device by bypassing conventional motor output pathways of nerves and muscles. Therefore they could provide a new communication and control option for paralyzed patients. Modern BCI technology is essentially based on techniques for the classification of single-trial brain signals. Here we present a novel technique that allows the simultaneous optimization of a spatial and a spectral filter enhancing discriminability rates of multichannel EEG single-trials. The evaluation of 60 experiments involving 22 different subjects demonstrates the significant superiority of the proposed algorithm over to its classical counterpart: the median classification error rate was decreased by 11%. Apart from the enhanced classification, the spatial and/or the spectral filter that are determined by the algorithm can also be used for further analysis of the data, e.g., for source localization of the respective brain rhythms.

The Berlin Brain-Computer Interface: EEG-based communication without subject training.

The Berlin Brain-Computer Interface (BBCI) project develops a noninvasive BCI system whose key features are 1) the use of well-established motor competences as control paradigms, 2) high-dimensional features from 128-channel electroencephalogram (EEG), and 3) advanced machine learning techniques. As reported earlier, our experiments demonstrate that very high information transfer rates can be achieved using the readiness potential (RP) when predicting the laterality of upcoming left- versus right-hand movements in healthy subjects. A more recent study showed that the RP similarily accompanies phantom movements in arm amputees, but the signal strength decreases with longer loss of the limb. In a complementary approach, oscillatory features are used to discriminate imagined movements (left hand versus right hand versus foot). In a recent feedback study with six healthy subjects with no or very little experience with BCI control, three subjects achieved an information transfer rate above 35 bits per minute (bpm), and further two subjects above 24 and 15 bpm, while one subject could not achieve any BCI control. These results are encouraging for an EEG-based BCI system in untrained subjects that is independent of peripheral nervous system activity and does not rely on evoked potentials even when compared to results with very well-trained subjects operating other BCI systems.

Towards adaptive classification for BCI.

Non-stationarities are ubiquitous in EEG signals. They are especially apparent in the use of EEG-based brain-computer interfaces (BCIs): (a) in the differences between the initial calibration measurement and the online operation of a BCI, or (b) caused by changes in the subject's brain processes during an experiment (e.g. due to fatigue, change of task involvement, etc). In this paper, we quantify for the first time such systematic evidence of statistical differences in data recorded during offline and online sessions. Furthermore, we propose novel techniques of investigating and visualizing data distributions, which are particularly useful for the analysis of (non-)stationarities. Our study shows that the brain signals used for control can change substantially from the offline calibration sessions to online control, and also within a single session. In addition to this general characterization of the signals, we propose several adaptive classification schemes and study their performance on data recorded during online experiments. An encouraging result of our study is that surprisingly simple adaptive methods in combination with an offline feature selection scheme can significantly increase BCI performance.