Christopher Wilke

Graph analysis of epileptogenic networks in human partial epilepsy

Purpose:  The current gold standard for the localization of the cortical regions responsible for the initiation and propagation of the ictal activity is through the use of invasive electrocorticography (ECoG). This method is utilized to guide surgical intervention in cases of medically intractable epilepsy by identifying the location and extent of the epileptogenic focus. Recent studies have proposed mechanisms in which the activity of epileptogenic cortical networks, rather than discrete focal sources, contributes to the generation of the ictal state. If true, selective modulation of key network components could be employed for the prevention and termination of the ictal state.

Electrophysiological Imaging of Brain Activity and Connectivity—Challenges and Opportunities

Unlocking the dynamic inner workings of the brain continues to remain a grand challenge of the 21st century. To this end, functional neuroimaging modalities represent an outstanding approach to better understand the mechanisms of both normal and abnormal brain functions. The ability to image brain function with ever increasing spatial and temporal resolution has made a significant leap over the past several decades. Further delineation of functional networks could lead to improved understanding of brain function in both normal and diseased states. This paper reviews recent advancements and current challenges in dynamic functional neuroimaging techniques, including electrophysiological source imaging, multimodal neuroimaging integrating fMRI with EEG/MEG, and functional connectivity imaging.

Defecting or Not Defecting: How to “Read” Human Behavior during Cooperative Games by EEG Measurements

Understanding the neural mechanisms responsible for human social interactions is difficult, since the brain activities of two or more individuals have to be examined simultaneously and correlated with the observed social patterns. We introduce the concept of hyper-brain network, a connectivity pattern representing at once the information flow among the cortical regions of a single brain as well as the relations among the areas of two distinct brains. Graph analysis of hyper-brain networks constructed from the EEG scanning of 26 couples of individuals playing the Iterated Prisoners Dilemma reveals the possibility to predict non-cooperative interactions during the decision-making phase. The hyper-brain networks of two-defector couples have significantly less inter-brain links and overall higher modularity—i.e., the tendency to form two separate subgraphs—than couples playing cooperative or tit-for-tat strategies. The decision to defect can be “read” in advance by evaluating the changes of connectivity pattern in the hyper-brain network.

Neocortical seizure foci localization by means of a directed transfer function method

Purpose:  Determination of the origin of extratemporal neocortical onset seizures is often challenging due to the rapid speed at which they propagate throughout the cortex. Typically, these patients are poor surgical candidates and many times experience recurrences of seizure activity following resection of the assumed seizure focus.

Estimation of Time-Varying Connectivity Patterns Through the Use of an Adaptive Directed Transfer Function

Frequency-derived identification of the propagation of information between brain regions has quickly become a popular area in the neurosciences. Of the various techniques used to study the propagation of activation within the central nervous system, the directed transfer function (DTF) has been well used to explore the functional connectivity during a variety of brain states and pathological conditions. However, the DTF method assumes the stationarity of the neural electrical signals and the time invariance of the connectivity among different channels over the investigated time window. Such assumptions may not be valid in the abnormal brain signals such as seizures and interictal spikes in epilepsy patients. In the present study, we have developed an adaptive DTF (ADTF) method through the use of a multivariate adaptive autoregressive model to study the time-variant propagation of seizures and interictal spikes in simulated electrocorticogram (ECoG) networks. The time-variant connectivity reconstruction is achieved by the Kalman filter algorithm, which can incorporate time-varying state equations. We study the performance of the proposed method through simulations with various propagation models using either sample seizures or interictal spikes as the source waveform. The present results suggest that the new ADTF method correctly captures the temporal dynamics of the propagation models, while the DTF method cannot, and even returns erroneous results in some cases. The present ADTF method was tested in real epileptiform ECoG data from an epilepsy patient, and the ADTF results are consistent with the clinical assessments performed by neurologists.

Imaging the Social Brain by Simultaneous Hyperscanning during Subject Interaction

Advances in neuroelectric recordings and computational tools allow investigation of interactive brain activity and connectivity in a group of subjects engaged in social interactions.

Identification of epileptogenic foci from causal analysis of ECoG interictal spike activity.

OBJECTIVE In patients with intractable epilepsy, the use of interictal spikes as surrogate markers of the epileptogenic cortex has generated significant interest. Previous studies have suggested that the cortical generators of the interictal spikes are correlated with the epileptogenic cortex as identified from the ictal recordings. We hypothesize that causal analysis of the functional brain networks during interictal spikes are correlated with the clinically-defined epileptogenic zone. METHODS We employed a time-varying causality measure, the adaptive directed transfer function (ADTF), to identify the cortical sources of the interictal spike activity in eight patients with medically intractable neocortical-onset epilepsy. The results were then compared to the foci identified by the epileptologists. RESULTS In all eight patients, the majority of the ADTF-calculated source activity was observed within the clinically-defined SOZs. Furthermore, in three of the five patients with two separate epileptogenic foci, the calculated source activity was correlated with both cortical sites. CONCLUSIONS The ADTF method identified the cortical sources of the interictal spike activity as originating from the same cortical locations as the recorded ictal activity. SIGNIFICANCE Evaluation of the sources of the cortical networks obtained during interictal spikes may provide information as to the generators underlying the ictal activity.

Dynamic imaging of ictal oscillations using non-invasive high-resolution EEG

Scalp electroencephalography (EEG) has been established as a major component of the pre-surgical evaluation for epilepsy surgery. However, its ability to localize seizure onset zones (SOZ) has been significantly restricted by its low spatial resolution and indirect correlation with underlying brain activities. Here we report a novel non-invasive dynamic seizure imaging (DSI) approach based upon high-density EEG recordings. This novel approach was particularly designed to image the dynamic changes of ictal rhythmic discharges that evolve through time, space and frequency. This method was evaluated in a group of 8 epilepsy patients and results were rigorously validated using intracranial EEG (iEEG) (n=3) and surgical outcome (n=7). The DSI localized the ictal activity in concordance with surgically resected zones and ictal iEEG recordings in the cohort of patients. The present promising results support the ability to precisely and accurately image dynamic seizure activity from non-invasive measurements. The successful establishment of such a non-invasive seizure imaging modality for surgical evaluation will have a significant impact in the management of medically intractable epilepsy.

Interictal spike analysis of high density EEG in patients with partial epilepsy

OBJECTIVE The aim of this study is to investigate the use of interictal spikes to localize epileptogenic brain from noninvasive scalp EEG recordings in patients with medically intractable epilepsy. METHODS Source reconstructions were performed using a high density electrode montage and a low density electrode montage by means of a distributed source modeling method. The source of interictal spike activity was localized using both a realistic geometry boundary element method (BEM) head model and 3-shell spherical head model. RESULTS In the analysis of 7 patients, the high density electrode montage was found to provide results more consistent with the suspected region of epileptogenic brain identified for surgical resection using intracranial EEG recordings and structural MRI lesions, as compared to the spatial low density electrode montage used in routine clinical practice. Furthermore, the realistic geometry BEM head model provided better source localization. CONCLUSIONS Our results indicate the merits of using high density scalp EEG recordings and realistic geometry head modeling for source localization of interictal spikes in patients with partial epilepsy. SIGNIFICANCE The present results suggest further improvement of source localization accuracy of epileptogenic brain from interictal EEG recorded using high density scalp electrode montage and realistic geometry head models.

EEG source imaging: correlating source locations and extents with electrocorticography and surgical resections in epilepsy patients.

Summary: It is desirable to estimate epileptogenic zones with both location and extent information from noninvasive EEG. In the present study, the authors use a subspace source localization method (FINE), combined with a local thresholding technique, to achieve such tasks. The performance of this method was evaluated in interictal spikes from three pediatric patients with medically intractable partial epilepsy. The thresholded subspace correlation, which is obtained from FINE scanning, is a favorable marker, which implies the extents of current sources associated with epileptic activities. The findings were validated by comparing the results with invasive electrocorticographic (ECoG) recordings of interictal spike activity. The surgical resections in these three patients correlated well with the epileptogenic zones identified from both EEG sources and ECoG potential distributions. The value of the proposed noninvasive technique for estimating epileptiform activity was supported by satisfactory surgery outcomes.