The effect of propofol on effective brain networks.

OBJECTIVE: We compared the effective networks derived from Single Pulse Electrical Stimulation (SPES) in intracranial electrocorticography (ECoG) of awake epilepsy patients and while under general propofol-anesthesia to investigate the effect of propofol on these brain networks. METHODS: We included nine patients who underwent ECoG for epilepsy surgery evaluation. We performed SPES when the patient was awake (SPES-clinical) and repeated this under propofol-anesthesia during the surgery in which the ECoG grids were removed (SPES-propofol). We detected the cortico-cortical evoked potentials (CCEPs) with an automatic detector. We constructed two effective networks derived from SPES-clinical and SPES-propofol. We compared three network measures (indegree, outdegree and betweenness centrality), the N1-peak-latency and amplitude of CCEPs between the two effective networks. RESULTS: Fewer CCEPs were observed during SPES-propofol (median: 6.0, range: 0-29) compared to SPES-clinical (median: 10.0, range: 0-36). We found a significant correlation for the indegree, outdegree and betweenness centrality between SPES-clinical and SPES-propofol (respectively rs = 0.77, rs = 0.70, rs = 0.55, p < 0.001). The median N1-peak-latency increased from 22.0 ms during SPES-clinical to 26.4 ms during SPES-propofol. CONCLUSIONS: Our findings suggest that the number of effective network connections decreases, but network measures are only marginally affected. SIGNIFICANCE: The primary network topology is preserved under propofol.

Evoked versus spontaneous high frequency oscillations in the chronic electrocorticogram in focal epilepsy.

OBJECTIVE: Spontaneous high frequency oscillations (HFOs; ripples 80-250Hz, fast ripples (FRs) 250-500Hz) are biomarkers for epileptogenic tissue in focal epilepsy. Single pulse electrical stimulation (SPES) can evoke HFOs. We hypothesized that stimulation distinguishes pathological from physiological ripples and compared the occurrence of evoked and spontaneous HFOs within the seizure onset zone (SOZ) and eloquent functional areas. METHODS: Ten patients underwent SPES during 2048Hz electrocorticography (ECoG). Evoked HFOs in time-frequency plots and spontaneous HFOs were visually analyzed. We compared electrodes with evoked and spontaneous HFOs for: percentages in the SOZ, sensitivity and specificity for the SOZ, percentages in functional areas outside the SOZ. RESULTS: Two patients without spontaneous FRs showed evoked FRs in the SOZ. Percentages of evoked and spontaneous HFOs in the SOZ were similar (ripples 32:33%, p=0.77; FRs 43:48%, p=0.63), but evoked HFOs had generally a lower specificity (ripples 45:69%, p=0.02; FRs 83:92%, p=0.04) and higher sensitivity (ripples 85:70%, p=0.27; FRs 52:37%, p=0.05). More electrodes with evoked than spontaneous ripples were found in functional (54:30%, p=0.03) and 'silent' areas (57:27%, p=0.01) outside the SOZ. CONCLUSIONS: SPES can elicit SOZ-specific FRs in patients without spontaneous FRs, but activates ripples in all areas. SIGNIFICANCE: SPES is an alternative for waiting for spontaneous HFOs, but does not warrant exclusively pathological ripples.

High frequency oscillations and high frequency functional network characteristics in the intraoperative electrocorticogram in epilepsy.

OBJECTIVE: High frequency oscillations (HFOs; > 80 Hz), especially fast ripples (FRs, 250-500 Hz), are novel biomarkers for epileptogenic tissue. The pathophysiology suggests enhanced functional connectivity within FR generating tissue. Our aim was to determine the relation between brain areas showing FRs and 'baseline' functional connectivity within EEG networks, especially in the high frequency bands. METHODS: We marked FRs, ripples (80-250 Hz) and spikes in the electrocorticogram of 14 patients with refractory temporal lobe epilepsy. We assessed 'baseline' functional connectivity in epochs free of epileptiform events within these recordings, using the phase lag index. We computed the Eigenvector Centrality (EC) per channel in the FR and gamma band network. We compared EC between channels that did or did not show events at other moments in time. RESULTS: FR-band EC was higher in channels with than without spikes. Gamma-band EC was lower in channels with ripples and FRs. CONCLUSIONS: We confirmed previous findings of functional isolation in the gamma-band and found a first proof of functional integration in the FR-band network of channels covering presumed epileptogenic tissue. SIGNIFICANCE: 'Baseline' high-frequency network parameters might help intra-operative recognition of epileptogenic tissue without the need for waiting for events. These findings can increase our understanding of the 'architecture' of epileptogenic networks and help unravel the pathophysiology of HFOs.

Single Pulse Electrical Stimulation to identify epileptogenic cortex: Clinical information obtained from early evoked responses.

OBJECTIVE: Single Pulse Electrical Stimulation (SPES) probes epileptogenic cortex during electrocorticography. Two SPES responses are described: pathological delayed responses (DR, >100 ms) associated with the seizure onset zone (SOZ) and physiological early responses (ER, <100 ms) that map cortical connectivity. We analyzed properties of ERs, including frequencies >80 Hz, in the SOZ and seizure propagation areas. METHODS: We used data from 12 refractory epilepsy patients. SPES consisted of 10 pulses of 1 ms, 4-8 mA and 5s interval on adjacent electrodes pairs. Data were available at 2048 samples/s for six and 512 samples/s (22 bits) for eight patients and analyzed in the time-frequency (TF) and time-domain (TD). RESULTS: Electrodes with ERs were stronger associated with SOZ than non-SOZ electrodes. ERs with frequency content >80 Hz exist and are specific for SOZ channels. ERs evoked by stimulation of seizure onset electrodes were associated with electrodes involved in seizure propagation. CONCLUSION: Analysis of ERs can reveal aspects of pathology, manifested by association with seizure propagation and areas with high ER numbers that coincide with the SOZ. SIGNIFICANCE: Not only DRs, but also ERs could have clinical value for mapping epileptogenic cortex and help to unravel aspects of the epileptic network.

High frequency oscillations in intra-operative electrocorticography before and after epilepsy surgery.

OBJECTIVE: Removal of brain tissue showing high frequency oscillations (HFOs; ripples: 80-250Hz and fast ripples: 250-500Hz) in preresection electrocorticography (preECoG) in epilepsy patients seems a predictor of good surgical outcome. We analyzed occurrence and localization of HFOs in intra-operative preECoG and postresection electrocorticography (postECoG). METHODS: HFOs were automatically detected in one-minute epochs of intra-operative ECoG sampled at 2048Hz of fourteen patients. Ripple, fast ripple, spike, ripples on a spike (RoS) and not on a spike (RnoS) rates were analyzed in pre- and postECoG for resected and nonresected electrodes. RESULTS: Ripple, spike and fast ripple rates decreased after resection. RnoS decreased less than RoS (74% vs. 83%; p=0.01). Most fast ripples in preECoG were located in resected tissue. PostECoG fast ripples occurred in one patient with poor outcome. Patients with good outcome had relatively high postECoG RnoS rates, specifically in the sensorimotor cortex. CONCLUSIONS: Our observations show that fast ripples in intra-operative ECoG, compared to ripples, may be a better biomarker for epileptogenicity. Further studies have to determine the relation between resection of epileptogenic tissue and physiological ripples generated by the sensorimotor cortex. SIGNIFICANCE: Fast ripples in intra-operative ECoG can help identify the epileptogenic zone, while ripples might also be physiological.

Interictal magnetoencephalography and the irritative zone in the electrocorticogram.

Magnetoencephalography (MEG) is considered a useful tool for planning electrode placement for chronic intracranial subdural electrocorticography (ECoG) in candidates for epilepsy surgery or even as a substitute for ECoG. MEG recordings are usually interictal and therefore, at best, reflect the interictal ECoG. To estimate the clinical value of MEG, it is important to know how well interictal MEG reflects interictal activity in the ECoG. From 1998 to 2008, 38 candidates for ECoG underwent a 151-channel MEG recording and 3D magnetic resonance imaging as a part of their presurgical evaluation. Interictal MEG spikes were identified, clustered, averaged and modelled using the multiple signal classification algorithm and co-registered to magnetic resonance imaging. ECoG was continuously recorded with electrode grids and strips for approximately 1 week. In a representative sample of awake interictal ECoG, interictal spikes were identified and averaged. The different spikes were characterized and quantified using a combined amplitude and synchronous surface-area measure. The ECoG spikes were ranked according to this measure and plotted on the magnetic resonance imaging surface rendering. Interictal spikes in MEG and ECoG were allocated to a predefined anatomical brain region and an association analysis was performed. All interictal MEG spikes were associated with an interictal ECoG spike. Overall, 56% of all interictal ECoG spikes had an interictal MEG counterpart. The association between the two was >or=90% in the interhemispheric and frontal orbital region, approximately 75% in the superior frontal, central and lateral temporal regions, but only approximately 25% in the mesial temporal region. MEG is a reliable indicator of the presence of interictal ECoG spikes and can be used to plan intracranial electrode placements. However, a substantial number of interictal ECoG spikes are not detected by MEG, and therefore MEG cannot be considered a substitute for ECoG.

Reduction of the Ballistocardiogram Artifact in Simultaneous EEG-fMRI using ICA.

The recording of EEG signals during fMRI scanning is now technically feasible and safe. However, artifacts relating to pulsatile blood flow (the ballistocardiogram) may still be prominently present in EEG data recorded in the MRI magnet. The application of Independent Component Analysis (ICA) in order to reduce these artifacts off-line was investigated in three different types of EEG, one normal Visually Evoked Potential (VEP), one normal ongoing EEG in a normal subject and the EEG of an epilepsy patient showing abnormal transients in the EEG. Results show that ICA is effective in reducing these pulsation artifacts, but that remaining signal quality may be affected.

Measurement of the conductivity of skull, temporarily removed during epilepsy surgery.

The conductivity of the human skull plays an important role in source localization of brain activity, because it is low as compared to other tissues in the head. The value usually taken for the conductivity of skull is questionable. In a carefully chosen procedure, in which sterility, a stable temperature, and relative humidity were guaranteed, we measured the (lumped, homogeneous) conductivity of the skull in five patients undergoing epilepsy surgery, using an extended four-point method. Twenty-eight current configurations were used, in each of which the potential due to an applied current was measured. A finite difference model, incorporating the geometry of the skull and the electrode locations, derived from CT data, was used to mimic the measurements. The conductivity values found were ranging from 32 mS/m to 80 mS/m, which is much higher than the values reported in other studies. Causes for these higher conductivity values are discussed.