Impact of surrounding tissue-type and peri-electrode gap in stereoelectroencephalography guided (SEEG) radiofrequency thermocoagulation (RF-TC): a computational study.

PURPOSE: To use computational modeling to provide a complete and logical description of the electrical and thermal behavior during stereoelectroencephalography-guided (SEEG) radiofrequency thermo-coagulation (RF-TC). METHODS: A coupled electrical-thermal model was used to obtain the temperature distributions in the tissue during RF-TC. The computer model was first validated by an ex vivo model based on liver fragments and later used to study the impact of three different factors on the coagulation zone size: 1) the difference in the tissue surrounding the electrode (gray/white matter), 2) the presence of a peri-electrode gap occupied by cerebrospinal fluid (CSF), and 3) the energy setting used (power-duration). RESULTS: The model built for the experimental validation was able to predict both the evolution of impedance and the short diameter of the coagulation zone (error < 0.01 mm) reasonably well but overestimated the long diameter by 2 - 3 mm. After adapting the model to clinical conditions, the simulation showed that: 1) Impedance roll-off limited the coagulation size but involved overheating (around 100 °C); 2) The type of tissue around the contacts (gray vs. white matter) had a moderate impact on the coagulation size (maximum difference 0.84 mm), and 3) the peri-electrode gap considerably altered the temperature distributions, avoided overheating, although the diameter of the coagulation zone was not very different from the no-gap case (<0.2 mm). CONCLUSIONS: This study showed that computer modeling, especially subject- and scenario-specific modeling, can be used to estimate in advance the electrical and thermal performance of the RF-TC in brain tissue.

Unification of optimal targeting methods in transcranial electrical stimulation.

One of the major questions in high-density transcranial electrical stimulation (TES) is: given a region of interest (ROI) and electric current limits for safety, how much current should be delivered by each electrode for optimal targeting of the ROI? Several solutions, apparently unrelated, have been independently proposed depending on how "optimality" is defined and on how this optimization problem is stated mathematically. The least squares (LS), weighted LS (WLS), or reciprocity-based approaches are the simplest ones and have closed-form solutions. An extended optimization problem can be stated as follows: maximize the directional intensity at the ROI, limit the electric fields at the non-ROI, and constrain total injected current and current per electrode for safety. This problem requires iterative convex or linear optimization solvers. We theoretically prove in this work that the LS, WLS and reciprocity-based closed-form solutions are specific solutions to the extended directional maximization optimization problem. Moreover, the LS/WLS and reciprocity-based solutions are the two extreme cases of the intensity-focality trade-off, emerging under variation of a unique parameter of the extended directional maximization problem, the imposed constraint to the electric fields at the non-ROI. We validate and illustrate these findings with simulations on an atlas head model. The unified approach we present here allows a better understanding of the nature of the TES optimization problem and helps in the development of advanced and more effective targeting strategies.

Perspectives on Optimized Transcranial Electrical Stimulation Based on Spatial Electric Field Modeling in Humans.

Background: Transcranial electrical stimulation (tES) generates an electric field (or current density) in the brain through surface electrodes attached to the scalp. Clinical significance has been demonstrated, although with moderate and heterogeneous results partly due to a lack of control of the delivered electric currents. In the last decade, computational electric field analysis has allowed the estimation and optimization of the electric field using accurate anatomical head models. This review examines recent tES computational studies, providing a comprehensive background on the technical aspects of adopting computational electric field analysis as a standardized procedure in medical applications. Methods: Specific search strategies were designed to retrieve papers from the Web of Science database. The papers were initially screened based on the soundness of the title and abstract and then on their full contents, resulting in a total of 57 studies. Results: Recent trends were identified in individual- and population-level analysis of the electric field, including head models from non-neurotypical individuals. Advanced optimization techniques that allow a high degree of control with the required focality and direction of the electric field were also summarized. There is also growing evidence of a correlation between the computationally estimated electric field and the observed responses in real experiments. Conclusions: Computational pipelines and optimization algorithms have reached a degree of maturity that provides a rationale to improve tES experimental design and a posteriori analysis of the responses for supporting clinical studies.

Regional variations distinguish auditory from visual evoked potentials in healthy 4 week old piglets.

Objective.Evoked potentials (EP), measured using electroencephalographic (EEG) recordings provide an opportunity to monitor cognitive dysfunctions after neurological diseases or traumatic brain injury (TBI). The 4 week old piglet is an established model of paediatric TBI; therefore, healthy piglets were studied to establish feasibility of obtaining responses to auditory and visual stimuli. A secondary aim was to input the EEG data into a piglet computational model to localize the brain sources related to processing. We tested the hypotheses: (1) visual, auditory-standard, and auditory-target stimuli elicit responses, (2) there is an effect of stimulus type, day tested, and electrode region on EPs from EEG, (3) there is an effect of stimulus type, day tested, and brain region on localized sources from a computational model.Approach.Eleven 4 week old female piglets were fitted with a 32-electrode net and presented with a simple white light stimulus and an auditory oddball click train (70 standard; 30 target tones).Main results.N1 andP2 amplitudes were consistently observed for all stimulus types. Significant interaction effects between brain region and stimulus for EP and current density demonstrate that cognitive responses are specific to each modality with auditory localizing to the temporal region and visual to the occipital regions. There was a day effect where larger responses were found on the first day than day 2 and 3 and may be due to the novelty of the stimulus on the first day. Visual stimuli had largerP1 amplitudes and earlier latencies (P1,N1) than auditory which coincides with current density results at 50 ms where larger activations were observed for visual. At 85 ms, auditory had significantly larger current densities coincident with larger and longerN1 amplitudes and latencies than visual.Significance.Auditory and visual processing were successfully and consistently obtained in a porcine model and can be evaluated as a diagnostic assessment for TBI.

TMS intensity and focality correlation with coil orientation at three non-motor regions.

Objective. The aim of this study is to define the best coil orientations for transcranial magnetic stimulation (TMS) for three clinically relevant brain areas: pre-supplementary motor area (pre-SMA), inferior frontal gyrus (IFG), and posterior parietal cortex (PPC), by means of simulations in 12 realistic head models of the electric field (E-field).Methods. We computed the E-field generated by TMS in our three volumes of interest (VOI) that were delineated based on published atlases. We then analysed the maximum intensity and spatial focality for the normal and absolute components of the E-field considering different percentile thresholds. Lastly, we correlated these results with the different anatomical properties of our VOIs.Results. Overall, the spatial focality of the E-field for the three VOIs varied depending on the orientation of the coil. Further analysis showed that differences in individual brain anatomy were related to the amount of focality achieved. In general, a larger percentage of sulcus resulted in better spatial focality. Additionally, a higher normal E-field intensity was achieved when the coil axis was placed perpendicular to the predominant orientations of the gyri of each VOI. A positive correlation between spatial focality and E-field intensity was found for PPC and IFG but not for pre-SMA.Conclusions. For a rough approximation, better coil orientations can be based on the individual's specific brain morphology at the VOI. Moreover, TMS computational models should be employed to obtain better coil orientations in non-motor regions of interest.Significance. Finding better coil orientations in non-motor regions is a challenge in TMS and seeks to reduce interindividual variability. Our individualized TMS simulation pipeline leads to fewer inter-individual variability in the focality, likely enhancing the efficacy of the stimulation and reducing the risk of stimulating adjacent, non-targeted areas.

Source localization of epileptic spikes using Multiple Sparse Priors.

OBJECTIVE: To evaluate epileptic source estimation using multiple sparse priors (MSP) inverse method and high-resolution, individual electrical head models. METHODS: Accurate source localization is dependent on accurate electrical head models and appropriate inverse solvers. Using high-resolution, individual electrical head models in fifteen epilepsy patients, with surgical resection and clinical outcome as criteria for accuracy, performance of MSP method was compared against standardized low-resolution brain electromagnetic tomography (sLORETA) and coherent maximum entropy on the mean (cMEM) methods. RESULTS: The MSP method performed similarly to the sLORETA method and slightly better than the cMEM method in terms of success rate. The MSP and cMEM methods were more focal than sLORETA with the advantage of not requiring an arbitrary selection of a hyperparameter or thresholding of reconstructed current density values to determine focus. MSP and cMEM methods were better than sLORETA in terms of spatial dispersion. CONCLUSIONS: Results suggest that the three methods are complementary and could be used together. In practice, the MSP method will be easier to use and interpret compared to sLORETA, and slightly more accurate and faster than the cMEM method. SIGNIFICANCE: Source localization of interictal spikes from dense-array electroencephalography data has been shown to be a reliable marker of epileptic foci and useful for pre-surgical planning. The advantages of MSP make it a useful complement to other inverse solvers in clinical practice.

Improvements on spatial coverage and focality of deep brain stimulation in pre-surgical epilepsy mapping.

Objective.Electrical stimulation mapping (ESM) of the brain using stereo-electroencephalography (SEEG) intracranial electrodes, also known as depth-ESM (DESM), is being used as part of the pre-surgical planning for brain surgery in drug-resistant epilepsy patients. Typically, DESM consists in applying the electrical stimulation using adjacent contacts of the SEEG electrodes and in recording the EEG responses to those stimuli, giving valuable information of critical brain regions to better delimit the region to resect. However, the spatial extension or coverage of the stimulated area is not well defined even though the precise electrode locations can be determined from computed tomography images.Approach.We first conduct electrical simulations of DESM for different shapes of commercial SEEG electrodes showing the stimulation extensions for different intensities of injected current. We then evaluate the performance of DESM in terms of spatial coverage and focality on two realistic head models of real patients undergoing pre-surgical evaluation. We propose a novel strategy for DESM that consist in applying the current using contacts of different SEEG electrodes (x-DESM), increasing the versatility of DESM without implanting more electrodes. We also present a clinical case where x-DESM replicated the full semiology of an epilepsy seizure using a very low-intensity current injection, when typical adjacent DESM only reproduced partial symptoms with much larger intensities. Finally, we show one example of DESM optimal stimulation to achieve maximum intensity, maximum focality or intermediate solution at a pre-defined target, and one example of temporal interference in DESM capable of increasing focality in brain regions not immediately touching the electrode contacts.Main results.It is possible to define novel current injection patterns using contacts of different electrodes (x-DESM) that might improve coverage and/or focality, depending on the characteristics of the candidate brain. If individual simulations are not possible, we provide the estimated radius of stimulation as a function of the injected current and SEEG electrode brand as a reference for the community.Significance.Our results show that subject-specific electrical stimulations are a valuable tool to use in the pre-surgical planning to visualize the extension of the stimulated regions. The methods we present here are also applicable to pre-surgical planning of tumor resections and deep brain stimulation treatments.

Focal limbic sources create the large slow oscillations of the EEG in human deep sleep.

BACKGROUND: Initial observations with the human electroencephalogram (EEG) have interpreted slow oscillations (SOs) of the EEG during deep sleep (N3) as reflecting widespread surface-negative traveling waves that originate in frontal regions and propagate across the neocortex. However, mapping SOs with a high-density array shows the simultaneous appearance of posterior positive voltage fields in the EEG at the time of the frontal-negative fields, with the typical inversion point (apparent source) around the temporal lobe. METHODS: Overnight 256-channel EEG recordings were gathered from 10 healthy young adults. Individual head conductivity models were created using each participant's own structural MRI. Source localization of SOs during N3 was then performed. RESULTS: Electrical source localization models confirmed that these large waves were created by focal discharges within the ventral limbic cortex, including medial temporal and caudal orbitofrontal cortex. CONCLUSIONS: Although the functional neurophysiology of deep sleep involves interactions between limbic and neocortical networks, the large EEG deflections of deep sleep are not created by distributed traveling waves in lateral neocortex but instead by relatively focal limbic discharges.

Transcranial Electrical Stimulation targeting limbic cortex increases the duration of human deep sleep.

BACKGROUND: Researchers have proposed that impaired sleep may be a causal link in the progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Several recent findings suggest that enhancing deep sleep (N3) may improve neurological health in persons with MCI, and buffer the risk for AD. Specifically, Transcranial Electrical Stimulation (TES) of frontal brain areas, the inferred source of the Slow Oscillations (SOs) of N3 sleep, can extend N3 sleep duration and improve declarative memory for recently learned information. Recent work in our laboratory using dense array Electroencephalography (dEEG) localized the sources of SOs to anterior limbic sites - suggesting that targeting these sites with TES may be more effective for enhancing N3. METHODS: For the present study, we recruited 13 healthy adults (M = 42 years) to participate in three all-night sleep EEG recordings where they received low level (0.5 mA) TES designed to target anterior limbic areas and a sham stimulation (placebo). We used a convolutional neural network, trained and tested on professionally scored EEG sleep staging, to predict sleep stages for each recording. RESULTS: When compared to the sham session, limbic-targeted TES significantly increased the duration of N3 sleep. TES also significantly increased spectral power in the 0.5-1 Hz frequency band (relative to pre-TES epochs) in left temporoparietal and left occipital scalp regions compared to sham. CONCLUSION: These results suggest that even low-level TES, when specifically targeting anterior limbic sites, can increase deep (N3) sleep and thereby contribute to healthy sleep quality.

A novel bounded EIT protocol to generate inhomogeneous skull conductivity maps non-invasively.

Electrical Impedance Tomography (EIT) can be used to estimate the electrical properties of the head tissues in a parametric approach. This modality is called parametric EIT or bounded EIT (bEIT). Typical bEIT protocols alternate between several current injection patterns with two current injection electrodes each: one source and one sink ("1-to-1"), while the rest of the electrodes measure the resulting electric potential. Then, one value of conductivity per tissue (e.g. scalp and/or skull) is estimated independently for each current injection pair. With these protocols, it is difficult to obtain local estimates of the skull tissue. Thus, the grand average of the estimates obtained from each pair is assigned to each tissue modeling them as homogeneous. However, it is known that these tissues are inhomogeneous within the same subject. We propose the use of current injection patterns with one source and many sinks ("1to-N") located at the opposite side of the head to build individual and inhomogeneous skull conductivity maps. We validate the method with simulations and compare its performance with equivalent maps generated by using the classical "1-to-1" patterns. The map generated by the novel method shows better spatial correlation with the more conductive spongy bone presence.Clinical Relevance- The novel bEIT protocol allows to map individual head models with spatially resolved skull conductivities in vivo and non-invasively for use in electroencephalography (EEG) source localization, transcranial electrical stimulation (TES) dose calculations and TES pattern optimization, without the risk of ionizing radiation associated with computed tomography (CT) scans.

Skull Modeling Effects in Conductivity Estimates Using Parametric Electrical Impedance Tomography.

OBJECTIVE: To estimate scalp, skull, compact bone, and marrow bone electrical conductivity values based on electrical impedance tomography (EIT) measurements, and to determine the influence of skull modeling details on the estimates. METHODS: We collected EIT data with 62 current injection pairs and built five 6-8 million finite element (FE) head models with different grades of skull simplifications for four subjects, including three whose head models serve as Atlases in the scientific literature and in commercial equipment (Colin27 and EGI's Geosource atlases). We estimated electrical conductivity of the scalp, skull, marrow bone, and compact bone tissues for each current injection pair, each model, and each subject. RESULTS: Closure of skull holes in FE models, use of simplified four-layer boundary element method-like models, and neglecting the CSF layer produce an overestimation of the skull conductivity of 10%, 10%-20%, and 20%-30%, respectively (accumulated overestimation of 50%-70%). The average extracted conductivities are 288 ± 53 (the scalp), 4.3 ± 0.08 (the compact bone), and 5.5 ± 1.25 (the whole skull) mS/m. The marrow bone estimates showed large dispersion. CONCLUSION: Present EIT estimates for the skull conductivity are lower than typical literature reference values, but previous in vivo EIT results are likely overestimated due to the use of simpler models. SIGNIFICANCE: Typical literature values of 7-10 mS/m for skull conductivity should be replaced by the present estimated values when using detailed skull head models. We also provide subject specific conductivity estimates for widely used Atlas head models.

Transcranial Electrical Neuromodulation Based on the Reciprocity Principle.

A key challenge in multi-electrode transcranial electrical stimulation (TES) or transcranial direct current stimulation (tDCS) is to find a current injection pattern that delivers the necessary current density at a target and minimizes it in the rest of the head, which is mathematically modeled as an optimization problem. Such an optimization with the Least Squares (LS) or Linearly Constrained Minimum Variance (LCMV) algorithms is generally computationally expensive and requires multiple independent current sources. Based on the reciprocity principle in electroencephalography (EEG) and TES, it could be possible to find the optimal TES patterns quickly whenever the solution of the forward EEG problem is available for a brain region of interest. Here, we investigate the reciprocity principle as a guideline for finding optimal current injection patterns in TES that comply with safety constraints. We define four different trial cortical targets in a detailed seven-tissue finite element head model, and analyze the performance of the reciprocity family of TES methods in terms of electrode density, targeting error, focality, intensity, and directionality using the LS and LCMV solutions as the reference standards. It is found that the reciprocity algorithms show good performance comparable to the LCMV and LS solutions. Comparing the 128 and 256 electrode cases, we found that use of greater electrode density improves focality, directionality, and intensity parameters. The results show that reciprocity principle can be used to quickly determine optimal current injection patterns in TES and help to simplify TES protocols that are consistent with hardware and software availability and with safety constraints.