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 r s = 0.77, r s = 0.70, r s = 0.55, p &lt; 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.</p

Neocortical electrical stimulation for epilepsy: Closed-loop versus open-loop

The aim of this review is to evaluate whether open-loop or closed-loop neocortical electrical stimulation should be the preferred approach to manage seizures in intractable epilepsy.Twenty cases of open-loop neocortical stimulation with an implanted device have been reported, in 5 case studies. Closed-loop stimulation with an implanted device has been investigated in a larger number of patients in the RNS System clinical trials. With 230 patients enrolled at the start of the Long-term Treatment Trial, 115 remained at the last reported follow-up. Open-loop stimulation reduced seizure frequency in patients on average with over 90% compared to baseline. Closed-loop stimulation reduces seizure frequency with 60%–65%.Even though open-loop neocortical electrical stimulation has only been reported in 20 patients, and closed-loop in much a larger sample, evidence suggests that both approaches are effective in reducing seizures. It remains an open question which should be clinically preferred. Therefore, a head-to-head adaptive clinical study comparing both approaches is propose

Neocortical electrical stimulation for epilepsy : Closed-loop versus open-loop

The aim of this review is to evaluate whether open-loop or closed-loop neocortical electrical stimulation should be the preferred approach to manage seizures in intractable epilepsy. Twenty cases of open-loop neocortical stimulation with an implanted device have been reported, in 5 case studies. Closed-loop stimulation with an implanted device has been investigated in a larger number of patients in the RNS System clinical trials. With 230 patients enrolled at the start of the Long-term Treatment Trial, 115 remained at the last reported follow-up. Open-loop stimulation reduced seizure frequency in patients on average with over 90% compared to baseline. Closed-loop stimulation reduces seizure frequency with 60%–65%. Even though open-loop neocortical electrical stimulation has only been reported in 20 patients, and closed-loop in much a larger sample, evidence suggests that both approaches are effective in reducing seizures. It remains an open question which should be clinically preferred. Therefore, a head-to-head adaptive clinical study comparing both approaches is proposed

Evoked directional network characteristics of epileptogenic tissue derived from single pulse electrical stimulation

We investigated effective networks constructed from single pulse electrical stimulation (SPES) in epilepsy patients who underwent intracranial electrocorticography. Using graph analysis, we compared network characteristics of tissue within and outside the epileptogenic area. In 21 patients with subdural electrode grids (1cm interelectrode distance), we constructed a binary, directional network derived from SPES early responses (<100ms). We calculated in-degree, out-degree, betweenness centrality, the percentage of bidirectional, receiving and activating connections, and the percentage of connections toward the (non-)epileptogenic tissue for each node in the network. We analyzed whether these network measures were significantly different in seizure onset zone (SOZ)-electrodes compared to non-SOZ electrodes, in resected area (RA)-electrodes compared to non-RA electrodes, and in seizure free compared to not seizure-free patients. Electrodes in the SOZ/RA showed significantly higher values for in-degree and out-degree, both at group level, and at patient level, and more so in seizure-free patients. These differences were not observed for betweenness centrality. There were also more bidirectional and fewer receiving connections in the SOZ/RA in seizure-free patients. It appears that the SOZ/RA is densely connected with itself, with only little input arriving from non-SOZ/non-RA electrodes. These results suggest that meso-scale effective network measures are different in epileptogenic compared to normal brain tissue. Local connections within the SOZ/RA are increased and the SOZ/RA is relatively isolated from the surrounding cortex. This offers the prospect of enhanced prediction of epilepsy-prone brain areas using SPES

Dynamical neural network reconstruction based on stimulation data

Single-pulse electrical stimulation (SPES) during clinical intracranial electrocorticography (iEEG) monitoring allows active probing of epileptogenic tissue. Two electrodes are stimulated, and the responses at other electrodes are recorded.These responses show physiological early responses (ERs) and more epileptogenic delayed responses (DRs). Earlier, we have demonstrated that neural mass models also produce and explain these responses. Here we propose to combine neural masses to create individualized neural mass networks reproducing the measured responses.We first show a dynamical inventory of small interacting neural masses using simulations and bifurcation analysis. Here we vary parameters related to intrinsic excitability, connectivity strength and background input. Second, we fit networks of small artificial topology and four real patient networks changing those parameters. We find that the ERs are nearly all reproduced. For the DRs, we can fit them in the small networks but to a lesser extent for the patient data. The resulting models may be helpful to explore the effect of stimulation protocols and surgery

A Comparison of Evoked and Non-evoked Functional Networks

The growing interest in brain networks to study the brain's function in cognition and diseases has produced an increase in methods to extract these networks. Typically, each method yields a different network. Therefore, one may ask what the resulting networks represent. To address this issue we consider electrocorticography (ECoG) data where we compare three methods. We derive networks from on-going ECoG data using two traditional methods: cross-correlation (CC) and Granger causality (GC). Next, connectivity is probed actively using single pulse electrical stimulation (SPES). We compare the overlap in connectivity between these three methods as well as their ability to reveal well-known anatomical connections in the language circuit. We find that strong connections in the CC network form more or less a subset of the SPES network. GC and SPES are related more weakly, although GC connections coincide more frequently with SPES connections compared to non-existing SPES connections. Connectivity between the two major hubs in the language circuit, Broca's and Wernicke's area, is only found in SPES networks. Our results are of interest for the use of patient-specific networks obtained from ECoG. In epilepsy research, such networks form the basis for methods that predict the effect of epilepsy surgery. For this application SPES networks are interesting as they disclose more physiological connections compared to CC and GC networks

A Comparison of Evoked and Non-evoked Functional Networks

The growing interest in brain networks to study the brain’s function in cognition and diseases has produced an increase in methods to extract these networks. Typically, each method yields a different network. Therefore, one may ask what the resulting networks represent. To address this issue we consider electrocorticography (ECoG) data where we compare three methods. We derive networks from on-going ECoG data using two traditional methods: cross-correlation (CC) and Granger causality (GC). Next, connectivity is probed actively using single pulse electrical stimulation (SPES). We compare the overlap in connectivity between these three methods as well as their ability to reveal well-known anatomical connections in the language circuit. We find that strong connections in the CC network form more or less a subset of the SPES network. GC and SPES are related more weakly, although GC connections coincide more frequently with SPES connections compared to non-existing SPES connections. Connectivity between the two major hubs in the language circuit, Broca’s and Wernicke’s area, is only found in SPES networks. Our results are of interest for the use of patient-specific networks obtained from ECoG. In epilepsy research, such networks form the basis for methods that predict the effect of epilepsy surgery. For this application SPES networks are interesting as they disclose more physiological connections compared to CC and GC networks

Detailed view on slow sinusoidal, hemodynamic oscillations on the human brain cortex by Fourier transforming oxy/deoxy hyperspectral images

Slow sinusoidal, hemodynamic oscillations (SSHOs) around 0.1 Hz are frequently seen in mammalian and human brains. In four patients undergoing epilepsy surgery, subtle but robust fluctuations in oxy- and deoxyhemoglobin were detected using hyperspectral imaging of the cortex. These SSHOs were stationary during the entire 4 to 10 min acquisition time. By Fourier filtering the oxy- and deoxyhemoglobin time signals with a small bandwidth, SSHOs became visible within localized regions of the brain, with distinctive frequencies and a continuous phase variation within that region. SSHOs of deoxyhemoglobin appeared to have an opposite phase and 11% smaller amplitude with respect to the oxyhemoglobin SSHOs. Although the origin of SSHOs remains unclear, we find indications that the observed SSHOs may embody a local propagating hemodynamic wave with velocities in line with capillary blood velocities, and conceivably related to vasomotion and maintenance of adequate tissue perfusion. Hyperspectral imaging of the human cortex during surgery allow in-depth characterization of SSHOs, and may give further insight in the nature and potential (clinical) use of SSHOs

Detailed view on slow sinusoidal, hemodynamic oscillations on the human brain cortex by Fourier transforming oxy/deoxy hyperspectral images

Slow sinusoidal, hemodynamic oscillations (SSHOs) around 0.1 Hz are frequently seen in mammalian and human brains. In four patients undergoing epilepsy surgery, subtle but robust fluctuations in oxy- and deoxyhemoglobin were detected using hyperspectral imaging of the cortex. These SSHOs were stationary during the entire 4 to 10 min acquisition time. By Fourier filtering the oxy- and deoxyhemoglobin time signals with a small bandwidth, SSHOs became visible within localized regions of the brain, with distinctive frequencies and a continuous phase variation within that region. SSHOs of deoxyhemoglobin appeared to have an opposite phase and 11% smaller amplitude with respect to the oxyhemoglobin SSHOs. Although the origin of SSHOs remains unclear, we find indications that the observed SSHOs may embody a local propagating hemodynamic wave with velocities in line with capillary blood velocities, and conceivably related to vasomotion and maintenance of adequate tissue perfusion. Hyperspectral imaging of the human cortex during surgery allow in-depth characterization of SSHOs, and may give further insight in the nature and potential (clinical) use of SSHOs