A Computational Modeling Study to Investigate the Use of Epicranial Electrodes to Deliver Interferential Stimulation to Subcortical Regions

Background: Epicranial cortical stimulation (ECS) is a minimally invasive neuromodulation technique that works by passing electric current between subcutaneous electrodes positioned on the skull. ECS causes a stronger and more focused electric field in the cortex compared to transcranial electric stimulation (TES) where the electrodes are placed on the scalp. However, it is unknown if ECS can target deeper regions where the electric fields become relatively weak and broad. Recently, interferential stimulation (IF) using scalp electrodes has been proposed as a novel technique to target subcortical regions. During IF, two high, but slightly different, frequencies are applied which sum to generate a low frequency field (i.e., 10 Hz) at a target subcortical region. We hypothesized that IF using ECS electrodes would cause stronger and more focused subcortical stimulation than that using TES electrodes.Objective: Use computational modeling to determine if interferential stimulation-epicranial cortical stimulation (IF-ECS) can target subcortical regions. Then, compare the focality and field strength of IF-ECS to that of interferential Stimulation-transcranial electric stimulation (IF-TES) in the same subcortical region.Methods: A human head computational model was developed with 19 TES and 19 ECS disk electrodes positioned on a 10–20 system. After tetrahedral mesh generation the model was imported to COMSOL where the electric field distribution was calculated for each electrode separately. Then in MATLAB, subcortical targets were defined and the optimal configurations were calculated for both the TES and ECS electrodes.Results: Interferential stimulation using ECS electrodes can deliver stronger and more focused electric fields to subcortical regions than IF using TES electrodes.Conclusion: Interferential stimulation combined with ECS is a promising approach for delivering subcortical stimulation without the need for a craniotomy.

Arousal and Consciousness in Focal Seizures

Impaired consciousness during seizures severely affects quality of life for people with epilepsy but the mechanisms are just beginning to be understood. Consciousness is thought to involve large-scale brain networks, so it is puzzling that focal seizures often impair consciousness. Recent work investigating focal temporal lobe or limbic seizures in human patients and experimental animal models suggests that impaired consciousness is caused by active inhibition of subcortical arousal mechanisms. Focal limbic seizures exhibit decreased neuronal firing in brainstem, basal forebrain, and thalamic arousal networks, and cortical arousal can be restored when subcortical arousal circuits are stimulated during seizures. These findings open the possibility of restoring arousal and consciousness therapeutically during and following seizures by thalamic neurostimulation. When seizures cannot be stopped by existing treatments, targeted subcortical stimulation may improve arousal and consciousness, leading to improved safety and better psychosocial function for people with epilepsy.

Subcortical Stimulation with Tip of Ultrasound Aspirator

Background During resection of intrinsic brain tumors in eloquent areas, particularly under awake mapping, subcortical stimulation is mandatory to avoid irreversible deficits by damaging white fiber tracts. The current practice is to alternate between subcortical stimulation with an appropriate probe and resection of tumoral tissue with an ultrasound aspiration device. Switching between different devices induces supplementary movement and possible tissue trauma, loss of time, and inaccuracies in the localization of the involved area. Objective To use one device for both stimulation as well as a resecting tool. Methods The tip of different ultrasound aspiration devices is currently used for monopolar current transmission (e.g., for vessel coagulation in liver surgery). We use the same circuitry for monopolar subcortical stimulation when connected with the usual stimulator devices. Results We have applied this method since 2004 in over 500 patients during tumor resection with cortical and subcortical stimulation, mostly with awake language and motor monitoring. Conclusion A method is presented using existing stimulation and wiring devices by which simultaneous subcortical stimulation and ultrasonic aspiration are applied with the same tool. The accuracy, safety, and speed of intrinsic intracranial lesion resection can be improved when subcortical stimulation is applied.

Diffusion tractography for awake craniotomy: accuracy and factors affecting specificity

Introduction Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)’s sensitivity to predict morbidity after neurosurgical oncology treatment. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and after awake neurosurgery; (2) evaluate utility of early post-operative DT to predict recovery from post-surgical deficits. Methods We retrospectively reviewed our first 100 awake neurosurgery procedures using DT- neuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations. Post-operative DT data, available in 51 patients, were inspected for tract damage. Results 91 adult brain tumor patients (mean 49.2 years, 43 women) underwent 100 awake surgeries with subcortical stimulation between 2014 and 2019. Sensitivity and specificity of pre-operative DT predictions were 92.2% and 69.2%, varying among tracts. Post-operative deficits occurred after 41 procedures (39%), but were prolonged (> 3 months) in only 4 patients (4%). Post-operative DT in general confirmed surgical preservation of tracts. Post-operative DT anticipated complete recovery in a patient with supplementary motor area syndrome, and indicated infarct-related damage to corticospinal fibers associated with delayed, partial recovery in a second patient. Conclusions Pre-operative DT provided very accurate predictions of the spatial location of tracts in relation to a tumor. As expected, however, the presence of a tract did not inform its functional status, resulting in variable DT specificity among individual tracts. While prolonged deficits were rare, DT in the immediate post-operative period offered additional potential to monitor neurological deficits and anticipate recovery potential.

Intraoperative mapping of pre-central motor cortex and subcortex: a proposal for supplemental cortical and novel subcortical maps to Penfield’s motor homunculus

Penfield’s motor homunculus describes a caricaturised yet useful representation of the map of various body parts on the pre-central cortex. We propose a supplemental map of the clinically represented areas of human body in pre-central cortex and a novel subcortical corticospinal tract map. We believe this knowledge is essential for safe surgery in patients with eloquent brain lesions. A single-institution retrospective cohort study of patients who underwent craniotomy for motor eloquent lesions with intraoperative motor neuromonitoring (cortical and subcortical) between 2015 and 2020 was performed. All positive cortical and subcortical stimulation points were taken into account and cartographic maps were produced to demonstrate cortical and subcortical areas of motor representation and their configuration. A literature review in PubMed was performed. One hundred and eighty consecutive patients (58.4% male, 41.6% female) were included in the study with 81.6% asleep and 18.4% awake craniotomies for motor eloquent lesions (gliomas 80.7%, metastases 13.8%) with intraoperative cortical and subcortical motor mapping. Based on the data, we propose a supplemental clinical cortical and a novel subcortical motor map to the original Penfield’s motor homunculus, including demonstration of localisation of intercostal muscles both in the cortex and subcortex which has not been previously described. The supplementary clinical cortical and novel subcortical motor maps of the homunculus presented here have been derived from a large cohort of patients undergoing direct cortical and subcortical brain mapping. The information will have direct relevance for improving the safety and outcome of patients undergoing resection of motor eloquent brain lesions.

Predictors of stimulation-induced seizures during perirolandic glioma resection using intraoperative mapping techniques

Background: Intraoperative mapping techniques maximize safety and efficacy during perirolandic glioma resection but may induce seizures and limit the procedure. We aim to report the incidence and predictors of stimulation-induced seizures during mapping either patient is awake or under general anesthesia (GA). Methods: Retrospective analysis of 64 patients (40 awake and 24 GA) with perirolandic glioma underwent resection using intraoperative mapping techniques between 2014 and 2019. Preoperative data, operative details, postoperative neurological status, and extent of resection (EOR) were analyzed. Predictors of intraoperative seizures were assessed. Results: The mean cortical and subcortical stimulation intensities needed to evoke motor responses were significantly lower in awake cases than in GA patients (4.9 ± 0.42 vs. 8.9 ± 1.2 mA) and (8.3 ± 0.62 vs. 12.1 ± 1.1 mA), respectively (P = 0.01). Incidence of intraoperative seizures was lower but statistically non-significant in awake cases (10% vs. 12.5%) (P = 0.76). Preoperative multiple antiepileptic drugs (AEDs) (P = 0.03) and low-grade glioma (P = 0.04) were statistically significant predictors for intraoperative seizures. Mean EOR in awake cases was 92.03% and 90.05% in GA cases (P = 0.23). Postoperative deficits were permanent after 3 months only in 5% of awake patients versus 8.3% of GA group (P = 0.59). Conclusion: Awake craniotomy with intraoperative mapping can be done safely for perirolandic gliomas with lower but statistically nonsignificant incidence of intraoperative seizures and this could be attributed to statistically significant lower stimulation intensities required for mapping. Preoperative multiple AEDs and low-grade glioma are significant predictors for intraoperative seizures.

The role of diffusion tensor imaging and tractography in the surgical management of brainstem gliomas

OBJECTIVEDiffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) have the ability to noninvasively visualize changes in white matter tracts, as well as their relationships with lesions and other structures. DTI/DTT has been increasingly used to improve the safety and results of surgical treatment for lesions in eloquent areas, such as brainstem cavernous malformations. This study aimed to investigate the application value of DTI/DTT in brainstem glioma surgery and to validate the spatial accuracy of reconstructed corticospinal tracts (CSTs).METHODSA retrospective analysis was performed on 54 patients with brainstem gliomas who had undergone surgery from January 2016 to December 2018 at Beijing Tiantan Hospital. All patients underwent preoperative DTI and tumor resection with the assistance of DTT-merged neuronavigation and electrophysiological monitoring. Preoperative conventional MRI and DTI data were collected, and the muscle strength and modified Rankin Scale (mRS) score before and after surgery were measured. The surgical plan was created with the assistance of DTI/DTT findings. The accuracy of DTI/DTT was validated by performing direct subcortical stimulation (DsCS) intraoperatively. Multiple linear regression was used to investigate the relationship between quantitative parameters of DTI/DTT (such as the CST score and tumor-to-CST distance [TCD]) and postoperative muscle strength and mRS scores.RESULTSAmong the 54 patients, 6 had normal bilateral CSTs, 12 patients had unilateral CST impairments, and 36 had bilateral CSTs involved. The most common changes in the CSTs were deformation (n = 29), followed by deviation (n = 28) and interruption (n = 27). The surgical approach was changed in 18 cases (33.3%) after accounting for the DTI/DTT results. Among 55 CSTs on which DsCS was performed, 46 (83.6%) were validated as spatially accurate by DsCS. The CST score and TCD were significantly correlated with postoperative muscle strength (r = −0.395, p < 0.001, and r = 0.275, p = 0.004, respectively) and postoperative mRS score (r = 0.430, p = 0.001, and r = −0.329, p = 0.015, respectively). The CST score was independently linearly associated with postoperative muscle strength (t = −2.461, p = 0.016) and the postoperative mRS score (t = 2.052, p = 0.046).CONCLUSIONSDTI/DTT is a valuable tool in the surgical management of brainstem gliomas. With good accuracy, it can help optimize surgical planning, guide tumor resection, and predict the postoperative muscle strength and postoperative quality of life of patients.

Intraoperative mapping of pre-central motor cortex and subcortex: a proposal for supplemental cortical and novel subcortical maps to Penfield’s motor homunculus

Introduction: Penfield’s motor homunculus describes a caricaturised yet useful representation of the map of various body parts on the pre-central cortex. We propose a supplemental map of the clinically represented areas of human body in pre-central cortex and a novel subcortical corticospinal tract map that are accurate and essential for safe surgery in patients with eloquent brain lesions. Materials and methods: A single-institution retrospective cohort study of patients who underwent craniotomy for motor eloquent lesions with intraoperative motor neuromonitoring (cortical and subcortical) between 2015 and 2020 was performed. All positive cortical and subcortical stimulation points were taken into account and cartographic maps were produced to demonstrate cortical and subcortical areas of motor representation and their configuration. A literature review in PubMed was performed. Results: 180 patients (58.4% male, 41.6% female) were included in the study with 81.6% asleep and 18.4% awake craniotomies for motor eloquent lesions (gliomas 80.7%, metastases 13.8%) with intraoperative cortical and subcortical motor mapping. Based on the data, we propose a supplemental clinical cortical and a novel subcortical motor map to the original Penfield’s motor homunculus, including demonstration of localisation of intercostal muscles both in the cortex and subcortex which has not been previously described. Conclusion: The supplementary clinical cortical and novel subcortical motor maps of the homunculus presented here have been derived from a large cohort of patients undergoing direct cortical and subcortical brain mapping. The information will have direct relevance for improving the safety and outcome of patients undergoing resection of motor eloquent brain lesions.

Neurophysiologic Mapping of Thalamocortical Tract in Asleep Craniotomies: Promising Results From an Early Experience

BACKGROUND Subcortical mapping of the corticospinal tract has been extensively used during craniotomies under general anesthesia to achieve maximal resection while avoiding postoperative motor deficits. To our knowledge, similar methods to map the thalamocortical tract (TCT) have not yet been developed. OBJECTIVE To describe a neurophysiologic technique for TCT identification in 2 patients who underwent resection of frontoparietal lesions. METHODS The central sulcus (CS) was identified using the somatosensory evoked potentials (SSEP) phase reversal technique. Furthermore, monitoring of the cortical postcentral N20 and precentral P22 potentials was performed during resection. Subcortical electrical stimulation in the resection cavity was done using the multipulse train (case #1) and Penfield (case #2) techniques. RESULTS Subcortical stimulation within the postcentral gyrus (case #1) and in depth of the CS (case #2), resulted in a sudden drop in amplitudes in N20 (case #1) and P22 (case #2), respectively. In both patients, the potentials promptly recovered once the stimulation was stopped. These results led to redirection of the surgical plane with avoidance of damage of thalamocortical input to the primary somatosensory (case #1) and motor regions (case #2). At the end of the resection, there were no significant changes in the median SSEP. Both patients had no new long-term postoperative sensory or motor deficit. CONCLUSION This method allows identification of TCT in craniotomies under general anesthesia. Such input is essential not only for preservation of sensory function but also for feedback modulation of motor activity.