Armin Brandt

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.

Neural Activity in Human Hippocampal Formation Reveals the Spatial Context of Retrieved Memories

Remembrance of Places Past The hippocampus has two major roles in cognition. Place-responsive neurons form a context-sensitive cognitive map, firing more strongly when an animal traverses specific regions of its environment. Both humans and animals thus need the hippocampus to learn their way around novel environments. Similarly, the hippocampus is critical for our ability to remember a specific event in space and time. It has thus been suggested that the spatial and memory functions of the hippocampus reflect a common architecture. Recording from neurosurgical patients playing a virtual reality memory game, Miller et al. (p. 1111) found that the recall of events was indeed associated with reinstatement of the place-firing of neurons activated as the subjects navigated through the environment. Place cells in the human brain that fired at an object’s location are reactivated during spontaneous recall. In many species, spatial navigation is supported by a network of place cells that exhibit increased firing whenever an animal is in a certain region of an environment. Does this neural representation of location form part of the spatiotemporal context into which episodic memories are encoded? We recorded medial temporal lobe neuronal activity as epilepsy patients performed a hybrid spatial and episodic memory task. We identified place-responsive cells active during virtual navigation and then asked whether the same cells activated during the subsequent recall of navigation-related memories without actual navigation. Place-responsive cell activity was reinstated during episodic memory retrieval. Neuronal firing during the retrieval of each memory was similar to the activity that represented the locations in the environment where the memory was initially encoded.

Hippocampal Gamma Oscillations Increase with Memory Load

Although the hippocampus plays a crucial role in encoding and retrieval of contextually mediated episodic memories, considerable controversy surrounds the role of the hippocampus in short-term or working memory. To examine both hippocampal and neocortical contributions to working memory function, we recorded electrocorticographic activity from widespread cortical and subcortical sites as 20 neurosurgical patients performed working memory tasks. These recordings revealed significant increases in 48–90 Hz gamma oscillatory power with memory load for two classes of stimuli: letters and faces. Sites exhibiting gamma increases with memory load appeared primarily in the hippocampus and medial temporal lobe. These findings implicate gamma oscillatory activity in the maintenance of both letters and faces in working memory and provide the first direct evidence for modulation of hippocampal gamma oscillations as humans perform a working memory task.

Gamma Oscillations Distinguish True From False Memories

To test whether distinct patterns of electrophysiological activity prior to a response can distinguish true from false memories, we analyzed intracranial electroencephalographic recordings while 52 patients undergoing treatment for epilepsy performed a verbal free-recall task. These analyses revealed that the same pattern of gamma-band (28–100 Hz) oscillatory activity that predicts successful memory formation at item encoding—increased gamma power in the hippocampus, prefrontal cortex, and left temporal lobe—reemerges at retrieval to distinguish correct from incorrect responses. The timing of these oscillatory effects suggests that self-cued memory retrieval begins in the hippocampus and then spreads to the cortex. Thus, retrieval of true, as compared with false, memories induces a distinct pattern of gamma oscillations, possibly reflecting recollection of contextual information associated with past experience.

Do False Predictions of Seizures Depend on the State of Vigilance? A Report from Two Seizure-Prediction Methods and Proposed Remedies

Summary:  Purpose: Available seizure‐prediction algorithms are accompanied by high numbers of false predictions to achieve high sensitivity. Little is known about the extent to which changes in EEG dynamics contribute to false predictions. This study addresses potential causes and the circadian distribution of false predictions as well as their relation to the sleep–wake cycle.

Long‐term seizure outcome in 211 patients with focal cortical dysplasia

Focal cortical dysplasia (FCD) is currently recognized as the most common cause of neocortical pharmacoresistant epilepsy. Epilepsy surgery has become an increasingly successful treatment option. Herein, the largest patient cohort reported to date is analyzed regarding long‐term outcome and factors relevant for long‐term seizure control.

Application of a multivariate seizure detection and prediction method to non-invasive and intracranial long-term EEG recordings

OBJECTIVE Retrospective evaluation and comparison of performances of a multivariate method for seizure detection and prediction on simultaneous long-term EEG recordings from scalp and intracranial electrodes. METHODS Two multivariate techniques based on simulated leaky integrate-and-fire neurons were investigated in order to detect and predict seizures. Both methods were applied and assessed on 423h of EEG and 26 seizures in total, recorded simultaneously from the scalp and intracranially continuously over several days from six patients with pharmacorefractory epilepsy. RESULTS Features generated from simultaneous scalp and intracranial EEG data showed a similar dynamical behavior. Significant performances with sensitivities of up to 73%/62% for scalp/invasive EEG recordings given an upper limit of 0.15 false detections per hour were obtained. Up to 59%/50% of all seizures could be predicted from scalp/invasive EEG, given a maximum number of 0.15 false predictions per hour. A tendency to better performances for scalp EEG was obtained for the detection algorithm. CONCLUSIONS The investigated methods originally developed for non-invasive EEG were successfully applied to intracranial EEG. Especially, concerning seizure detection the method shows a promising performance which is appropriate for practical applications in EEG monitoring. Concerning seizure prediction a significant prediction performance is indicated and a modification of the method is suggested. SIGNIFICANCE This study evaluates simultaneously recorded non-invasive and intracranial continuous long-term EEG data with respect to seizure detection and seizure prediction for the first time.

Spatio-temporal patient–individual assessment of synchronization changes for epileptic seizure prediction

OBJECTIVE Abnormal synchronization of neurons plays a central role for the generation of epileptic seizures. Therefore, multivariate time series analysis techniques investigating relationships between the dynamics of different neural populations may offer advantages in predicting epileptic seizures. METHODS We applied a phase and a lag synchronization measure to a selected subset of multicontact intracranial EEG recordings and assessed changes in synchronization with respect to seizure prediction. RESULTS Patient individual results, group results, spatial aspects using focal and extra-focal electrode contacts as well as two evaluation schemes analyzing decreases and increases in synchronization were examined. Averaged sensitivity values of 60% are observed for a false prediction rate of 0.15 false predictions per hour, a seizure occurrence period of half an hour, and a prediction horizon of 10 min. For approximately half of all 21 patients, a statistically significant prediction performance is observed for at least one synchronization measure and evaluation scheme. CONCLUSIONS The results indicate that synchronization changes in the EEG dynamics preceding seizures can be used for seizure prediction. Nevertheless, the underlying pathogenic mechanisms differ and both decreases and increases in synchronization may precede epileptic seizures depending on the structures investigated. SIGNIFICANCE The prediction method, optimized values of intervention times, as well as preferred brain structures for the EEG recordings have to be determined for each patient individually offering the chance of a better patient-individual prediction performance.

Seizure induced cardiac asystole in epilepsy patients undergoing long term video-EEG monitoring

Ictal-related cardiac asystole is supposed to be a risk factor for sudden unexpected death in epilepsy (SUDEP). We retrospectively analyzed the occurrence of ictal asystole in 2003 epilepsy patients undergoing long-term video EEG/ECG monitoring from 1/1999 to 6/2010 at the Freiburg epilepsy centre. Seven patients had cardiac arrest with a duration of at least 3s; 6 ictal, one postictal. In all patients, the temporal lobe was involved in ictal activity based on neurophysiological investigations or morphological lesion. Whereas asystole was self-limited in six cases, one patient with insular seizure origin had to undergo cardiopulmonary resuscitation. Interestingly, also patients with a short history of epilepsy, low seizure frequency and under treatment in monotherapy showed episodes of asystole. In all cases, even with brief cardiac arrest, asystole was associated with subsequent EEG flattening. In conclusion, ictal asystole is a rare event even in a population undergoing major changes in antiepileptic medication. Temporal lobe epilepsy was associated with a risk for asystole; cardiac arrest also occurred in patients who, based on their history, might have not been considered at elevated risk for SUDEP.

Seizure and cognitive outcomes of epilepsy surgery in infancy and early childhood

AIMS To investigate seizure and developmental outcomes following epilepsy surgery in very young children and determine their predictive factors. METHODS We retrospectively reviewed the clinical data, surgical variables, and outcomes of 30 children under 3 years of age that underwent resection for refractory focal epilepsy in our institution in 2001-2011. RESULTS Seizure onset was in the first year of life in 27 (90%) cases and mean age at surgery was 20 months (range 5-33.6). Pathology consisted of cortical malformations in 24 (80%) cases, glioneuronal tumour and infarction with or without cortical dysplasia in three (10%) cases each. Morbidity was comparable with older paediatric cohorts. At 1-11.6 year follow-up (mean 4.1) 21 of 30 (70%) children achieved seizure freedom (Engel I), six (20%) demonstrated worthwhile improvement (Engel II/III) and three (10%) did not benefit from surgery (Engel IV). Intralobar lesionectomy more often resulted in seizure freedom than multilobar or hemispheric surgery. The abundance of non-regional interictal and ictal EEG findings did not preclude seizure freedom. Presurgical developmental impairment was established in 25 of 28 (89%) children; its severity correlated with longer epilepsy duration and determined postoperative developmental outcome. Developmental progress was established in 26 out of 28 (93%) children following surgery, showing stabilized trajectories rather than catch-up. CONCLUSIONS Resective surgery in very young children is safe and effective in terms of seizure control and developmental progress. Our findings underline the importance of early intervention in order to timely stop seizures and their deleterious effects on the developing brain.