Andreas Schulze-Bonhage

The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission†

Purpose:  Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities.

Incidence and Mechanisms of Cardiorespiratory Arrests in Epilepsy Monitoring Units (MORTEMUS): A Retrospective Study.

BACKGROUND Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. METHODS Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. FINDINGS 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time. FUNDING Commission of European Affairs of the International League Against Epilepsy.

Prediction of arm movement trajectories from ECoG-recordings in humans

Electrocorticographic (ECoG) signals have been shown to contain reliable information about the direction of arm movements and can be used for on-line cursor control. These findings indicate that the ECoG is a potential basis for a brain-machine interface (BMI) for application in paralyzed patients. However, previous approaches to ECoG-BMIs were either based on classification of different movement patterns or on a voluntary modulation of spectral features. For a continuous multi-dimensional BMI control, the prediction of complete movement trajectories, as it has already been shown for spike data and local field potentials (LFPs), would be a desirable addition for the ECoG, too. Here, we examined ECoG signals from six subjects with subdurally implanted ECoG-electrodes during continuous two-dimensional arm movements between random target positions. Our results show that continuous trajectories of 2D hand position can be approximately predicted from the ECoG recorded from hand/arm motor cortex. This indicates that ECoG signals, related to body movements, can directly be transferred to equivalent controls of an external effector for continuous BMI control.

Reset of human neocortical oscillations during a working memory task

Both amplitude and phase of rhythmic slow-wave electroencephalographic activity are physiological correlates of learning and memory in rodents. In humans, oscillatory amplitude has been shown to correlate with memory; however, the role of oscillatory phase in human memory is unknown. We recorded intracranial electroencephalogram from human cortical and hippocampal areas while subjects performed a short-term recognition memory task. On each trial, a series of four list items was presented followed by a memory probe. We found agreement across trials of the phase of oscillations in the 7- to 16-Hz range after randomly timed stimulus events, evidence that these events either caused a phase shift in the underlying oscillation or initiated a new oscillation. Phase locking in this frequency range was not generally associated with increased poststimulus power, suggesting that stimulus events reset the phase of ongoing oscillations. Different stimulus classes selectively modulated this phase reset effect, with topographically distinct sets of recording sites exhibiting preferential reset to either probe items or to list items. These findings implicate the reset of brain oscillations in human working memory.

Signal quality of simultaneously recorded invasive and non-invasive EEG.

Both invasive and non-invasive electroencephalographic (EEG) recordings from the human brain have an increasingly important role in neuroscience research and are candidate modalities for medical brain-machine interfacing. It is often assumed that the major artifacts that compromise non-invasive EEG, such as caused by blinks and eye movement, are absent in invasive EEG recordings. Quantitative investigations on the signal quality of simultaneously recorded invasive and non-invasive EEG in terms of artifact contamination are, however, lacking. Here we compared blink related artifacts in non-invasive and invasive EEG, simultaneously recorded from prefrontal and motor cortical regions using an approach suitable for detection of small artifact contamination. As expected, we find blinks to cause pronounced artifacts in non-invasive EEG both above prefrontal and motor cortical regions. Unexpectedly, significant blink related artifacts were also found in the invasive recordings, in particular in the prefrontal region. Computing a ratio of artifact amplitude to the amplitude of ongoing brain activity, we find that the signal quality of invasive EEG is 20 to above 100 times better than that of simultaneously obtained non-invasive EEG. Thus, while our findings indicate that ocular artifacts do exist in invasive recordings, they also highlight the much better signal quality of invasive compared to non-invasive EEG data. Our findings suggest that blinks should be taken into account in the experimental design of ECoG studies, particularly when event related potentials in fronto-anterior brain regions are analyzed. Moreover, our results encourage the application of techniques for reducing ocular artifacts to further optimize the signal quality of invasive EEG.

Movement related activity in the high gamma range of the human EEG.

Electrocorticographic (ECoG) recordings obtained using intracranially implanted electrodes in epilepsy patients indicate that high gamma band (HGB) activity of sensorimotor cortex is focally increased during voluntary movement. These movement related HGB modulations may play an important role in sensorimotor cortex function. It is however currently not clear to what extent this type of neural activity can be detected using non-invasive electroencephalography (EEG) and how similar HGB responses in healthy human subjects are to those observed in epilepsy patients. Using the same arm reaching task, we have investigated spectral power changes both in intracranial ECoG recordings in epilepsy patients and in non-invasive EEG recordings optimized for detecting HGB activity in healthy subjects. Our results show a common HGB response pattern both in ECoG and EEG recorded above the sensorimotor cortex contralateral to the side of arm movement. In both cases, HGB activity increased around movement onset in the 60-90 Hz range and became most pronounced at reaching movement end. Additionally, we found EEG HGB activity above the frontal midline possibly generated by the anterior supplementary motor area (SMA), a region that was however not covered by the intracranial electrodes used in the present study. In summary, our findings show that HGB activity from human sensorimotor cortex can be non-invasively detected in healthy subjects using EEG, opening a new perspective for investigating the role of high gamma range neuronal activity both in function and dysfunction of the human cortical sensorimotor network.

Functional organization of the human anterior insular cortex

The human insular cortex is involved in a wide range of functions including motor control, language, and homeostatic regulation. Little is known, however, how these functions are topographically organized in the insular cortex and how they are functionally related to the amygdala, which is anatomically connected to the insular cortex. We have investigated these questions by conducting an activation likelihood estimate (ALE) meta-analysis of previously published neuroimaging studies reporting insula effects. We find auditory and language tasks to preferentially activate an area in the dorsal part of the anterior insular cortex (AIC). Motor tasks involving both the upper and lower extremity reproducibly activated a posterior AIC region, adjacent to the sulcus centralis insulae (SCI). Significant co-activation with the probabilistically defined amygdala was located in the ventral AIC where also responses related to peripheral physiological changes were repeatedly reported. These findings show that the human AIC is a functionally differentiated brain region. The dorsal region of the AIC may be involved in auditory-motor integration, while the ventral part of the AIC may interface the amygdala with insular regions involved in the regulation of physiological changes related to emotional states. Thus, the present findings provide insights into the organization of human AIC and a methodological approach that may be further used to refine the emerging functional map of the insular cortex.

Enhanced visualization of blurred gray–white matter junctions in focal cortical dysplasia by voxel-based 3D MRI analysis

PURPOSE Focal cortical dysplasia (FCD), a frequent cause of partial epilepsy, is often associated with blurring of the gray-white matter junction in magnetic resonance images (MRI). To improve the recognition and delineation of FCD we developed a novel voxel-based image post-processing method for enhanced visualization of blurred gray-white matter junctions. METHODS Using standard algorithms of statistical parametric mapping software (SPM99) a T1-weighted MRI volume data set is normalized and segmented. The distribution of gray and white matter is analyzed on a voxelwise basis and compared with a normal database. Based on this analysis, a three-dimensional feature map is created which highlights brain areas with blurred gray-white matter transition. This method was applied to the MRI data of 25 epilepsy patients with histologically proven FCD. RESULTS In 18/25 patients the new feature maps clearly showed that the dysplastic lesions were accompanied by blurring of the gray-white matter junction. Combined with a formerly published method of voxel-based 3D MRI analysis, 21/25 FCD lesions were shown to be associated with either blurring or abnormal extension of gray matter beyond the normal cortical ribbon, including four cases with lesions not or incompletely recognized on conventional MRI. CONCLUSIONS The MRI post-processing presented here improves the visualization of FCD and may increase the diagnostic yield of MRI. Thereby, it provides a valuable additional diagnostic tool in the presurgical evaluation of epilepsy patients.

Testing statistical significance of multivariate time series analysis techniques for epileptic seizure prediction

Nonlinear time series analysis techniques have been proposed to detect changes in the electroencephalography dynamics prior to epileptic seizures. Their applicability in practice to predict seizure onsets is hampered by the present lack of generally accepted standards to assess their performance. We propose an analytic approach to judge the prediction performance of multivariate seizure prediction methods. Statistical tests are introduced to assess patient individual results, taking into account that prediction methods are applied to multiple time series and several seizures. Their performance is illustrated utilizing a bivariate seizure prediction method based on synchronization theory.

Decoding natural grasp types from human ECoG

Electrocorticographic (ECoG) signals have been successfully used to provide information about arm movement direction, individual finger movements and even continuous arm movement trajectories. Thus, ECoG has been proposed as a potential control signal for implantable brain-machine interfaces (BMIs) in paralyzed patients. For the neuronal control of a prosthesis with versatile hand/arm functions, it is also necessary to successfully decode different types of grasping movements, such as precision grip and whole-hand grip. Although grasping is one of the most frequent and important hand movements performed in everyday life, until now, the decoding of ECoG activity related to different grasp types has not been systematically investigated. Here, we show that two different grasp types (precision vs. whole-hand grip) can be reliably distinguished in natural reach-to-grasp movements in single-trial ECoG recordings from the human motor cortex. Self-paced movement execution in a paradigm accounting for variability in grasped object position and weight was chosen to create a situation similar to everyday settings. We identified three informative signal components (low-pass-filtered component, low-frequency and high-frequency amplitude modulations), which allowed for accurate decoding of precision and whole-hand grips. Importantly, grasp type decoding generalized over different object positions and weights. Within the frontal lobe, informative signals predominated in the precentral motor cortex and could also be found in the right hemispheres homologue of Brocas area. We conclude that ECoG signals are promising candidates for BMIs that include the restoration of grasping movements.