A three-layer MRI-based head phantom for experimental validation of tES simulations

Transcranial electric stimulation (tES) is being investigated for the relief of seizures in medically refractory epilepsy patients. In a quest to optimize the electrode placement and current for improvement of the outcome, we are investigating the exploitation of the pre-stimulation planning using finite element simulations based on individual anatomy from MRI [RM1] scans. A crucial step is validating the stimulation modeling accuracy, but commercial setups for validation do not exist.Hereto, we developed a three-layer head phantom, consisting of skin, skull, and brain tissue, that captures the crucial anatomical features and provides a convenient way of verifying the induced electric fields. It also enables systematic characterization of the uncertainties and variations in conductivity and anatomy. Experiments on the three-layer phantom bridge the gap between simulations and clinical practice since they also allow for using clinical hardware and electrodes.The developed phantom consists of an agar and salt brain layer, a graphite-doped polyurethane skull, and a skin layer made from agar gel with a different conductivity. In this way the solid skull separates the two gel layers, preventing possible ion drift over the layers. The anatomy is based on the ICBM 152 linear model, an average of 152 MRI scans, which enables us to intuitively link measurements and simulations. To perform the systematic characterization experiments, hardware and software were designed in-house. This allows for stimulations and measurements on the phantom in a cheap and modular way. The designed hardware consists of a PID-controlled tES stimulator, which can deliver 4 mA with a frequency up to 100 Hz, and a four-channel differential sensing board based on the OpenBCI Ganglion board.A realistic and modular phantom expands the possibilities of preclinical tES research by providing a tool to validate electric field simulations as well as experiment with clinical hardware and anatomical variations

Physiological consequences of abnormal connectivity in a developmental epilepsy

Objective Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities. Methods We employed transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recording in 8 patients with epilepsy from periventricular nodular heterotopia and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single-pulse stimulation from different cortical regions. Results Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in 1 subject revealed that the generator of abnormal TMS-evoked activity overlapped with the spike and seizure onset zone. Interpretation Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS-EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions

Evaluating Robustness of Brain Stimulation Biomarkers for depression:A Systematic Review of MRI and EEG Studies

Non-invasive brain stimulation (NIBS) treatments have gained considerable attention as a potential therapeutic intervention for psychiatric disorders. The identification of reliable biomarkers for predicting clinical response to NIBS has been a major focus of research in recent years. Neuroimaging techniques, such as electroencephalography (EEG) and (functional) magnetic resonance imaging (fMRI), have been used to identify potential biomarkers that could predict response to NIBS. However, identifying clinically actionable brain biomarkers requires robustness. In this systematic review, we aimed to summarize the current state of brain biomarker research for NIBS in depression, focusing only on well-powered studies (N=88) and/or studies that aimed at independently replicating prior findings, either successfully or unsuccessfully. A total of 220 studies were initially identified, of which 18 MRI studies and 18 EEG studies adhered to the inclusion criteria, all focused on repetitive transcranial magnetic stimulation treatment in depression. After reviewing the included studies, we found the following MRI and EEG biomarkers to be most robust: 1) fMRI-based functional connectivity between the dorsolateral prefrontal cortex and subgenual anterior cingulate cortex, 2) fMRI-based network connectivity, 3) task-induced EEG frontal-midline theta, and 4) EEG individual alpha frequency. Future prospective studies should further investigate the clinical actionability of these specific EEG and MRI biomarkers to bring biomarkers closer to clinical reality

Combining EEG and MRI data to personalize neurostimulation for focal epilepsy:an open-source software implementation

Personalizing the stimulation location of transcranial neurostimulation based on the subject's individual anatomy is becoming more important in clinical research. In the case of focal epilepsy, there often is a clear target to stimulate that can be found by analysis of multi-modal clinical data, including EEG source localization. Hypothesizing its clinical importance, we developed a procedure to exploit the spatial target information and optimize the tDCS montage such that the induced electric field has maximum overlap with the target. This could be beneficial to tailor the treatment on a per-patient basis, so every patient will be stimulated with the intended field at the intended location. While commercial workflows for personalized tDCS exist, a flexible, easy-to-use and open-source software that integrates EEG source localization and tDCS optimization techniques in one application was not yet available. To support open research, we therefore combined open-source solutions into an intuitive MATLAB software tool for (clinical) research purposes. This tool interfaces intuitively with other open-source tools: the Brain-storm package (EEG processing and source localization) and SimNibs (neurostimulation optimization). The most relevant parameters such as tissue conductivity and optimization constraints can be changed via the user interface. Based on MRI data, a head segmentation can be made and converted into a FEM model for both software's. Clinical targets can be defined in subjects pace or calculated via source localization. A tDCS montage can be optimized for this target using either patch electrodes or high-definition electrodes. The field maps for the optimized montage and the field distribution histograms are presented in the user interface. Based on these analyses, the tool produces a report in which the flow from input to output can be analyzed. In this way, clinical researchers worldwide are offered a research tool for streamlining the research into dose-effect relations, as well as personalization possibilities.<br/

Left prefrontal neuronavigated electrode localization in tDCS : 10-20 EEG system versus MRI-guided neuronavigation

Transcranial direct current stimulation (tDCS) involves positioning two electrodes at specifically targeted locations on the human scalp. In neuropsychiatric research, the anode is often placed over the left dorsolateral prefrontal cortex (DLPFC), while the cathode is positioned over a contralateral cephalic region above the eye, referred-to as the supraorbital region. Although the 10-20 EEG system is frequently used to locate the DLPFC, due to inter-subject brain variability, this method may lack accuracy. Therefore, we compared in forty participants left DLPFC-localization via the 10-20 EEG system to MRI-guided neuronavigation. In one participant, with individual electrode positions in close proximity to the mean electrode position across subjects, we also investigated whether distinct electrode localizations were associated with different tDCS-induced electrical field distributions. Furthermore, we aimed to examine which neural region is targeted when placing the reference-electrode on the right supraorbital region. Compared to the 10-20 EEG system, MRI-guided neuronavigation localizes the DLPFC-targeting anode more latero-posteriorly, targeting the middle prefrontal gyrus. tDCS-induced electric fields (n=1) suggest that both localization methods induce significantly different electric fields in distinct brain regions. Considering the frequent application of tDCS as a neuropsychiatric treatment, an evaluation and direct comparison of the clinical efficacy of targeting methods is warranted