Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study.

OBJECTIVE: In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger-causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls. METHODS: Twenty LTLE, 20 RTLE, and 20 healthy controls underwent a resting-state high-density EEG recording. Source activity was obtained for 82 regions of interest (ROIs) using an individual head model and a distributed linear inverse solution. Granger-causal modeling was applied to the source signals of all ROIs. The directed functional connectivity results were compared between groups and correlated with clinical parameters (duration of the disease, age of onset, age, and learning and mood impairments). RESULTS: We found that: (1) patients had significantly reduced connectivity from regions concordant with the default-mode network; (2) there was a different network pattern in patients versus controls: the strongest connections arose from the ipsilateral hippocampus in patients and from the posterior cingulate cortex in controls; (3) longer disease duration was associated with lower driving from contralateral and ipsilateral mediolimbic regions in RTLE; (4) aging was associated with a lower driving from regions in or close to the piriform cortex only in patients; and (5) outflow from the anterior cingulate cortex was lower in patients with learning deficits or depression compared to patients without impairments and to controls. SIGNIFICANCE: Resting-state network reorganization in the absence of IEDs strengthens the view of chronic and progressive network changes in TLE. These resting-state connectivity alterations could constitute an important biomarker of TLE, and hold promise for using EEG recordings without IEDs for diagnosis or prognosis of this disorder.

Dynamic directed interictal connectivity in left and right temporal lobe epilepsy.

OBJECTIVE: There is increasing evidence that epileptic activity involves widespread brain networks rather than single sources and that these networks contribute to interictal brain dysfunction. We investigated the fast-varying behavior of epileptic networks during interictal spikes in right and left temporal lobe epilepsy (RTLE and LTLE) at a whole-brain scale using directed connectivity. METHODS: In 16 patients, 8 with LTLE and 8 with RTLE, we estimated the electrical source activity in 82 cortical regions of interest (ROIs) using high-density electroencephalography (EEG), individual head models, and a distributed linear inverse solution. A multivariate, time-varying, and frequency-resolved Granger-causal modeling (weighted Partial Directed Coherence) was applied to the source signal of all ROIs. A nonparametric statistical test assessed differences between spike and baseline epochs. Connectivity results between RTLE and LTLE were compared between RTLE and LTLE and with neuropsychological impairments. RESULTS: Ipsilateral anterior temporal structures were identified as key drivers for both groups, concordant with the epileptogenic zone estimated invasively. We observed an increase in outflow from the key driver already before the spike. There were also important temporal and extratemporal ipsilateral drivers in both conditions, and contralateral only in RTLE. A different network pattern between LTLE and RTLE was found: in RTLE there was a much more prominent ipsilateral to contralateral pattern than in LTLE. Half of the RTLE patients but none of the LTLE patients had neuropsychological deficits consistent with contralateral temporal lobe dysfunction, suggesting a relationship between connectivity changes and cognitive deficits. SIGNIFICANCE: The different patterns of time-varying connectivity in LTLE and RTLE suggest that they are not symmetrical entities, in line with our neuropsychological results. The highest outflow region was concordant with invasive validation of the epileptogenic zone. This enhanced characterization of dynamic connectivity patterns could better explain cognitive deficits and help the management of epilepsy surgery candidates.

Surgically relevant localization of the central sulcus with high-density somatosensory-evoked potentials compared with functional magnetic resonance imaging.

BACKGROUND: Resection of abnormal brain tissue lying near the sensorimotor cortex entails precise localization of the central sulcus. Mapping of this area is achieved by applying invasive direct cortical electrical stimulation. However, noninvasive methods, particularly functional magnetic resonance imaging (fMRI), are also used. As a supplement to fMRI, localization of somatosensory-evoked potentials (SEPs) recorded with an electroencephalogram (EEG) has been proposed, but has not found its place in clinical practice. OBJECTIVE: To assess localization accuracy of the hand somatosensory cortex with SEP source imaging. METHODS: We applied electrical source imaging in 49 subjects, recorded with high-density EEG (256 channels). We compared it with fMRI in 18 participants and with direct cortical electrical stimulation in 6 epileptic patients. RESULTS: Comparison of SEP source imaging with fMRI indicated differences of 3 to 8 mm, with the exception of the mesial-distal orientation, where variances of up to 20 mm were found. This discrepancy is explained by the fact that the source maximum of the first SEP peak is localized deep in the central sulcus (area 3b), where information initially arrives. Conversely, fMRI showed maximal signal change on the lateral surface of the postcentral gyrus (area 1), where sensory information is integrated later in time. Electrical source imaging and fMRI showed mean Euclidean distances of 13 and 14 mm, respectively, from the contacts where electrocorticography elicited sensory phenomena of the contralateral upper limb. CONCLUSION: SEP source imaging, based on high-density EEG, reliably identifies the depth of the central sulcus. Moreover, it is a simple, flexible, and relatively inexpensive alternative to fMRI.

Localization of the epileptogenic tuber with electric source imaging in patients with tuberous sclerosis.

PURPOSE: Patients with tuberous sclerosis complex (TSC) often suffer from medically refractory epilepsy. Despite the multifocality of the disease, resection of the most epileptogenic tuber can lead to major improvement of seizure control. Therefore, non-invasive imaging methods are needed for detecting epileptogenic sources. We assessed the utility of electric source imaging (ESI) in the presurgical work-up of TSC patients and its combination with Positron Emission Tomography (PET) and ictal/interictal Single Photon Emission Computed Tomography (SISCOM). METHODS: Thirteen patients underwent high density ESI (8/13) and/or low density ESI (13/13). We investigated the concordance between ESI, PET, SISCOM and the resection area in the 11 operated patients (nine seizure-free). RESULTS: High resolution ESI was partially or completely concordant with the resected area in 5/5 seizure free patients. Low resolution ESI was partially or completely concordant in 7/9 seizure free patients. PET and SPECT were concordant (partially or completely) in 8/9 and 6/9 cases, respectively. We found multifocal ESI sources in 2/9 seizure free patients, marked multifocal PET hypometabolism in 3/9 and multifocal SISCOM in 4/9. The region of concordant ESI and PET accurately predicted the dominant epileptogenic source in 6/9 patients. The same was true for concordant ESI and SISCOM in 4/9 patients, whereas the coregistration of only PET and SISCOM was insufficient in 3/9 successfully operated cases. The combination of all three imaging modalities could successfully identify the resection area in all but one patient with a favorable post-operation outcome. CONCLUSION: ESI is an important tool for the pre-surgical evaluation of TSC patients. It complements PET and SPECT results and can improve the management of candidates for surgery when integrated with electro-clinical information.

Electric source imaging of interictal activity accurately localises the seizure onset zone.

OBJECTIVE: It remains controversial whether interictal spikes are a surrogate of the seizure onset zone (SOZ). Electric source imaging (ESI) is an increasingly validated non-invasive approach for localising the epileptogenic focus in patients with drug-resistant epilepsy undergoing evaluation for surgery, using high-density scalp EEG and advanced source localisation algorithms that include the patient's own MRI. Here we investigate whether localisation of interictal spikes by ESI provides valuable information on the SOZ. METHODS: In 38 patients with focal epilepsy who later underwent intracranial EEG monitoring, we performed ESI of interictal spikes recorded with 128-256-channel EEG. We measured the distance between the ESI maximum and the nearest intracranial electrodes in the SOZ and irritative zone (IZ, the source of interictal spikes). The resection of the region harbouring the ESI maximum was correlated to surgical outcome. RESULTS: The median distance from the ESI maximum to the nearest electrode involved in the SOZ was 17 mm (IQR 8-27). The IZ and SOZ colocalised in most patients (median distance 0 mm, IQR 0-14), supporting the notion that localising interictal spikes is a valid surrogate for the SOZ. There was no difference in accuracy among patients with temporal or extratemporal epilepsy. In the 32 patients who underwent resective surgery, including the ESI maximum in the resection correlated with favourable outcome (p=0.03). CONCLUSIONS: Localisation of interictal spikes provides an excellent estimate of the SOZ in the majority of patients. ESI should be taken into account for the management of patients undergoing intracranial recordings.

Noninvasive language mapping in patients with epilepsy or brain tumors.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has become part of routine brain mapping in patients with epilepsy or tumor undergoing resective surgery. However, robust localization of crucial functional areas is required. OBJECTIVE: To establish a simple, short fMRI task that reliably localizes crucial language areas in individual patients who undergo respective surgery. METHODS: fMRI was measured during an 8-minute auditory semantic decision task in 28 healthy controls and 35 consecutive patients who had focal epilepsy or a brain tumor. Nineteen underwent resective surgery. Group and individual analyses were performed. Results in patients were compared with postsurgical language outcome and electrocortical stimulation when available. RESULTS: fMRI activations concordant with the anterior and posterior language areas were found in 96% and 89% of the controls, respectively. The anterior and posterior language areas were both activated in 93% of the patients. These results were concordant with electrocortical stimulation results in 5 patients. Transient postsurgical language deficits were found in 2 patients in whom surgery was performed in the vicinity of the fMRI activations or who had postsurgical complications implicating areas of fMRI activations. CONCLUSION: The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects. It appears to be a valuable complementary tool for surgical planning of epileptogenic foci and of brain tumors.

An electrophysiological study of conscious visual perception using progressively degraded stimuli.

Previous event-related potential (ERP) studies have provided mixed results regarding the earliest manifestations of conscious visual report. One possible explanation for the results could be that conscious visual perception emerges progressively rather than appearing as a binary transition. In the present study, we used electrical neuroimaging to identify the stages of processing that lead to the successful conscious identification of a briefly presented degraded stimulus. Grayscale images of faces and butterflies were presented for 16 ms and their visibility was manipulated by means of random image structure evolution (RISE). Three levels of RISE image distortions were used for each image. First, we determined an individual detection threshold of 50% for each subject. We then added two control conditions, namely fully degraded stimuli and stimuli that yielded 80% detection. Topographic ERP analyses revealed distinct effects for identified and unidentified stimuli at the threshold of detection. Four stages were observed that distinguished successful from unsuccessful stimulus identification. This shows that the events associated with conscious perception occurs at several distinct stages in time starting as early as 220 ms after stimulus presentation, rather than translating as a single temporal event and includes marked top-down activations when identification becomes difficult.

Temporal dynamics of awareness for facial identity revealed with ERP.

In this study, we investigated the scalp recorded event-related potential (ERP) responses related to visual awareness. A backward masking procedure was performed while high-density EEG recordings were carried out. Subjects were asked to detect a familiar face, presented at durations that varied parametrically between 16 and 266 ms. ERPs were computed and awareness was assessed using a sensitivity measure from signal detection theory (d'). Modifications in the electrical scalp topographies were found to reflect visual awareness of the stimulus. In particular, an early map topography was found to emerge progressively around 230 ms, showing a pattern of increase similar to the measure of visual awareness. This was followed by an increase in duration of a second, P300-like map. Source localisation for the early awareness-related topography revealed the activation of a distributed network of brain areas including frontal and temporo-occipital regions. Our results suggest that conscious experience emerges in parallel with the activation of a specific neural network that occurs in a time window beginning from about 200 ms.