Paving the Way for Memory Enhancement: Development and Examination of a Neurofeedback System Targeting the Medial Temporal Lobe.

Neurofeedback (NF) shows promise in enhancing memory, but its application to the medial temporal lobe (MTL) still needs to be studied. Therefore, we aimed to develop an NF system for the memory function of the MTL and examine neural activity changes and memory task score changes through NF training. We created a memory NF system using intracranial electrodes to acquire and visualise the neural activity of the MTL during memory encoding. Twenty trials of a tug-of-war game per session were employed for NF and designed to control neural activity bidirectionally (Up/Down condition). NF training was conducted with three patients with drug-resistant epilepsy, and we observed an increasing difference in NF signal between conditions (Up-Down) as NF training progressed. Similarities and negative correlation tendencies between the transition of neural activity and the transition of memory function were also observed. Our findings demonstrate NF's potential to modulate MTL activity and memory encoding. Future research needs further improvements to the NF system to validate its effects on memory functions. Nonetheless, this study represents a crucial step in understanding NF's application to memory and provides valuable insights into developing more efficient memory enhancement strategies.

Intracranial Neurofeedback Modulating Neural Activity in the Mesial Temporal Lobe During Memory Encoding: A Pilot Study.

Removal of the mesial temporal lobe (MTL) is an established surgical procedure that leads to seizure freedom in patients with intractable MTL epilepsy; however, it carries the potential risk of memory damage. Neurofeedback (NF), which regulates brain function by converting brain activity into perceptible information and providing feedback, has attracted considerable attention in recent years for its potential as a novel complementary treatment for many neurological disorders. However, no research has attempted to artificially reorganize memory functions by applying NF before resective surgery to preserve memory functions. Thus, this study aimed (1) to construct a memory NF system that used intracranial electrodes to feedback neural activity on the language-dominant side of the MTL during memory encoding and (2) to verify whether neural activity and memory function in the MTL change with NF training. Two intractable epilepsy patients with implanted intracranial electrodes underwent at least five sessions of memory NF training to increase the theta power in the MTL. There was an increase in theta power and a decrease in fast beta and gamma powers in one of the patients in the late stage of memory NF sessions. NF signals were not correlated with memory function. Despite its limitations as a pilot study, to our best knowledge, this study is the first to report that intracranial NF may modulate neural activity in the MTL, which is involved in memory encoding. The findings provide important insights into the future development of NF systems for the artificial reorganization of memory functions.

Efficient volume-based localization and automatic labeling of intracranial depth electrodes.

Background: The accurate localization and anatomical labeling of intracranial depth electrodes are crucial for stereoelectroencephalography (SEEG) recordings and the interpretation of results in patients with epilepsy. The laborious electrode localization procedure requires an efficient and easy-to-use pipeline. Thus, we developed a useful tool, which we called the depth electrode localizer (DELLO), to automatically identify and label depth electrode contacts with ease. Methods: The DELLO is an open-source package developed in MATLAB (MathWorks). It was specifically fine-tuned to expedite the localization of depth electrodes. The basic procedures include preoperative magnetic resonance imaging (MRI) and postoperative computed tomography coregistration, intensity threshold electrode spatial sampling, the hierarchical clustering of electrode samples, and gray-matter and automatic anatomical labeling (AAL). The DELLO also has a graphical user interface (GUI) that can be used to review the results. The only manual intervention procedures are the identification of the target (tip) and entry point of each electrode and the naming of the clustered electrode contact groups, which generally take ~5 min per case. The coordinates of each contact were recorded in individual spaces and were also transformed in standard space by applying a volume-based deformation field. To validate the performance of the current method, 7 patients with epilepsy were retrospectively included in the analysis. Results: A total of 80 depth electrodes, including 1,030 contacts from the 7 patients with epilepsy, were localized. All the procedures functioned well, and the entire process was robust and intuitive. Among the 1,030 contacts, 746 (72.43%) were labeled as inside the gray matter. The gray-matter and AAL accuracy rates were 95.83% and 90.78%, respectively, over all contacts. Conclusions: The DELLO is an integrated tool that was designed to semi-automatically localize and label intracranial depth electrodes. It is open source and freely available. Given its high accuracy and efficiency, the DELLO could facilitate SEEG interpretation and be used in SEEG-based cognitive neuroscience studies.

Posterior cerebral artery stenosis related to implanted intracranial electrodes for temporal lobe epilepsy: A case report.

INTRODUCTION: Intracranial electroencephalography is a crucial diagnostic technique for epilepsy surgery, though it is associated with a range of complications, including infection, intracranial hemorrhage, increased intracranial pressure, and cerebral infarction. This case study presents an uncommon occurrence of stenosis of the left posterior cerebral artery (PCA) following intracranial electrode implantation. CASE PRESENTATION: A woman in her thirties with drug-resistant focal impaired awareness seizures underwent implantation of subdural and depth electrodes on the bilateral temporal lobes to lateralize seizure onset. A left anterior-temporal lobectomy was performed based on the evaluation results. Following the resection of the hippocampus, stenosis of the left PCA, with a pinched appearance, was observed. Postoperatively, extensive cerebral edema in the bilateral temporal lobes and a defect in the left PCA were detected on magnetic resonance (MR) imaging. MR imaging performed the day after surgery showed cerebral infarction in the left medial temporal lobe and left lateral thalamus. A video review indicated that surgical manipulation was not the cause of vascular stenosis. MR angiography one week later confirmed the recanalization of the PCA. DISCUSSION: We surmised that the subdural electrodes inserted along the middle skull base might have induced the PCA stenosis or spasms. The patient did not experience any significant sequelae, with no episodes of seizures for more than five years after surgery. CONCLUSION: It is essential to note that subdural grid electrodes placed in the medial temporal lobe can cause vascular stenosis, albeit with an extremely rare occurrence.

Usefulness of Intraoperative Electrocorticography for the Localization of Epileptogenic Zones.

Intraoperative electrocorticography (iECoG) is widely performed to identify irritative zones in the cortex during brain surgery; however, several limitations (e.g., short recording times and the effects of general anesthesia) reduce its effectiveness. The present study aimed to evaluate the utility of iECoG for localizing epileptogenic zones. We compared the results of iECoG and chronic electrocorticography (cECoG) in 25 patients with refractory epilepsy. Subdural electrodes were implanted with iECoG under general anesthesia (2% sevoflurane). cECoG recordings were performed for 3-14 days. The distribution of iECoG spikes was compared with cECoG spike, seizure onset zone, and resection areas. The concordance patterns of each distribution were classified into four patterns: Group 1: No spike in iECoG, Group 2: concordant (2a: iECoG smaller, 2b: iECoG larger, Group 3: discordant >50%). The concordance rate of interictal spikes, seizure onset zones, and resection areas were 88.0% (Group 2a: 72.0%, Group 2b: 16.0%), 70.0% (Group 2a: 25.0%, Group 2b: 45.0%), and 81.0% (Group 2a: 42.9%, Group 2b: 38.1%), respectively. The resection of iECoG spike areas significantly correlated with good surgical outcomes. The indication and limitations of iECoG need to be realized, and the complementary use of iECoG and cECoG may enhance clinical utility.

Cortical recordings reveal hidden early signs of recovery following traumatic brain injury: A case report.

Prognosticating recovery of consciousness after severe traumatic brain injury (TBI) is a difficult task. Understanding the mechanism of recovery of consciousness in these patients will undoubtedly help clarify this issue. Recent research has underscored the importance of electrophysiological data in characterizing the state of the brain during this period of unconsciousness. Here, we investigated cortical electrophysiological recordings from a single TBI patient and discovered that high-frequency activity associated with the return of consciousness reappeared in a spatiotemporal fashion. We observed a shift toward higher frequencies first in the anterior cingulate cortex, and then later in the dorsolateral prefrontal cortex. This finding suggests that recovery may originate in more internal cortices and progress to superficial ones. Although this observation occurred in a single patient, it points to a potential mechanism for recovery of normal cortical activity in the return of consciousness following TBI.

Corrigendum: LeGUI: A Fast and Accurate Graphical User Interface for Automated Detection and Anatomical Localization of Intracranial Electrodes.

[This corrects the article DOI: 10.3389/fnins.2021.769872.].

LeGUI: A Fast and Accurate Graphical User Interface for Automated Detection and Anatomical Localization of Intracranial Electrodes.

Accurate anatomical localization of intracranial electrodes is important for identifying the seizure foci in patients with epilepsy and for interpreting effects from cognitive studies employing intracranial electroencephalography. Localization is typically performed by coregistering postimplant computed tomography (CT) with preoperative magnetic resonance imaging (MRI). Electrodes are then detected in the CT, and the corresponding brain region is identified using the MRI. Many existing software packages for electrode localization chain together separate preexisting programs or rely on command line instructions to perform the various localization steps, making them difficult to install and operate for a typical user. Further, many packages provide solutions for some, but not all, of the steps needed for confident localization. We have developed software, Locate electrodes Graphical User Interface (LeGUI), that consists of a single interface to perform all steps needed to localize both surface and depth/penetrating intracranial electrodes, including coregistration of the CT to MRI, normalization of the MRI to the Montreal Neurological Institute template, automated electrode detection for multiple types of electrodes, electrode spacing correction and projection to the brain surface, electrode labeling, and anatomical targeting. The software is written in MATLAB, core image processing is performed using the Statistical Parametric Mapping toolbox, and standalone executable binaries are available for Windows, Mac, and Linux platforms. LeGUI was tested and validated on 51 datasets from two universities. The total user and computational time required to process a single dataset was approximately 1 h. Automatic electrode detection correctly identified 4362 of 4695 surface and depth electrodes with only 71 false positives. Anatomical targeting was verified by comparing electrode locations from LeGUI to locations that were assigned by an experienced neuroanatomist. LeGUI showed a 94% match with the 482 neuroanatomist-assigned locations. LeGUI combines all the features needed for fast and accurate anatomical localization of intracranial electrodes into a single interface, making it a valuable tool for intracranial electrophysiology research.

Investigation of displacement of intracranial electrode induced by focused ultrasound stimulation.

Transcranial focused ultrasound (tFUS) is an emerging neuromodulation technique to modulate brain activity non-invasively with high spatial specificity and focality. Given the influence of tFUS on brain activity, combining tFUS with multi-channel intracranial electrophysiological recordings enables monitoring of the activity of large populations of neurons with high temporal resolution. However, the physical interactions between tFUS and the electrode may affect a reliable assessment of neuronal activity, which remains poorly understood. In this paper, high-frequency ultrasound (HFUS) system was developed and integrated into tFUS neuromodulation system. The performance of the HFUS-based displacement tracking and analysis was evaluated by the theoretical analysis in the literature. The effects of various pressure levels on the displacements of the silicon-based microelectrode array in ex vivo brain tissue were investigated. The developed approach was capable of tracking and measuring the motion of a solid sphere in a tissue-mimicking phantom and measured displacements were comparable to theoretical predictions. The significant changes in the averaged peak displacements of the microelectrode array in ex vivo brain were observed with a pulse duration of 200 µs and a peak-to-peak pressure from 131 kPa at a center frequency of 500 kHz compared with the values from the negative control group. The present results demonstrate the relationship between several pressure levels and displacements of the microelectrode array in ex vivo brain through the developed approach. This approach can be used to determine a vibration-free threshold of ultrasound parameters in multi-channel intracranial recordings for a reliable assessment of electrophysiological activities of living neurons.

Cortical regions and networks of hyperkinetic seizures: Electrocorticography and diffusion tensor imaging study.

OBJECTIVE: The present study investigated the cortical areas and networks responsible for hyperkinetic seizures by analyzing invasive recordings and diffusion tensor imaging (DTI) tractography. METHODS: Seven patients with intractable focal epilepsy in whom hyperkinetic seizures were recorded during an invasive evaluation at Sapporo Medical University between January 2012 and March 2020 were enrolled in the present study. Intracranial recordings were analyzed to localize seizure-onset zones (SOZs) and symptomatogenic zones (spread areas at clinical onset). DTI was used to identify the subcortical fibers originating from SOZs. RESULTS: Ten SOZs were located in four areas: (1) the inferior parietal lobule (two SOZs in two patients), (2) temporo-occipital junction (three SOZs in two patients), (3) medial temporal area (three SOZs in three patients) and (4) medial/lateral frontal lobe (two SOZs in two patients). Symptomatogenic zones appeared to be the premotor area, basal temporal area, temporo-occipital junction, and the postcentral gyrus/supramarginal gyrus. The tractographic analysis revealed that the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MLF), arcuate fasciculus (AF)/superior longitudinal fasciculus (SLF) II, III, and cingulum bundle may be associated with hyperkinetic seizures. CONCLUSION: The present results suggest the cortical areas (the inferior parietal lobule, temporo-occipital junction, medial temporal area, and medial/lateral frontal lobe) and subcortical fibers (IFOF, ILF, MLF, AF/SLFII, III, and the cingulum bundle) responsible for generating hyperkinetic seizures.

Long-term mood, quality of life, and seizure freedom in intracranial EEG epilepsy surgery.

OBJECTIVES: To determine the long-term outcomes in patients undergoing intracranial EEG (iEEG) evaluation for epilepsy surgery in terms of seizure freedom, mood, and quality of life at St. Vincent's Hospital, Melbourne. METHODS: Patients who underwent iEEG between 1999 and 2016 were identified. Patients were retrospectively assessed between 2014 and 2017 by specialist clinic record review and telephone survey with standardized validated questionnaires for: 1) seizure freedom using the Engel classification; 2) Mood using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E); 3) Quality-of-life outcomes using the QOLIE-10 questionnaire. Summary statistics and univariate analysis were performed to investigate variables for significance. RESULTS: Seventy one patients underwent iEEG surgery: 49 Subdural, 14 Depths, 8 Combination with 62/68 (91.9%) of those still alive, available at last follow-up by telephone survey or medical record review (median of 8.2 years). The estimated epileptogenic zone was 62% temporal and 38% extra-temporal. At last follow-up, 69.4% (43/62) were Engel Class I and 30.6% (19/62) were Engel Class II-IV. Further, a depressive episode (NDDI-E > 15)was observed in 34% (16/47), while a 'better quality of life' (QOLIE-10 score < 25) was noted in 74% (31/42). Quality of life (p < 0.001) but not mood (p = 0.24) was associated with seizure freedom. SIGNIFICANCE: Long-term seizure freedom can be observed in patients undergoing complex epilepsy surgery with iEEG evaluation and is associated with good quality of life.

Misleading non-epileptic epileptiform activities on intracranial recordings.

Numerous non-epileptic physiological electroencephalographic (EEG) patterns morphologically mimic epileptiform activity. However, misleading non-epileptic findings of electrocorticography (ECoG) have not yet been examined in detail. The aim of the present study was to identify non-epileptic epileptiform ECoG findings. We retrospectively reviewed the intracranial recordings of 21 patients with intractable focal epilepsy who became seizure-free after a presurgical evaluation with subdural electrodes following resective surgeries at Sapporo Medical University between January 2014 and December 2018. Morphological epileptiform findings outside epileptogenic areas were judged as non-epileptic and analyzed. Seventeen areas in nine patients exhibited non-epileptic epileptiform activities. These areas were identified in the lateral temporal cortices, basal temporal areas, rolandic areas, and frontal lobe. Morphological patterns were classified into three types: 1) spiky oscillations, 2) isolated spiky activity, and 3) isolated fast activity. The normal cortex may exhibit non-epileptic epileptiform activities. These activities need to be carefully differentiated from real epileptic abnormalities to prevent the mislocalization of epileptogenic areas.

Threshold and distribution of afterdischarges with electrical cortical stimulation.

OBJECTIVE: The present study aimed to investigate the threshold and distribution of afterdischarges (ADs) with cortical electrical stimulation for functional brain mapping. METHOD: We retrospectively analyzed data from 11 patients with medically intractable epilepsy who underwent 50-Hz cortical electrical stimulation for functional mapping followed by resection. These patients became seizure free for more than six months. The threshold and distribution of ADs induced by the stimulation were evaluated. RESULTS: The median threshold was 6 mA (range: 2-15 mA) for the frontal lobe, 8 mA (3-15 mA) for the temporal lobe, 6 mA (2-15 mA) for the parietal lobe, and 6 mA (4-12 mA) for the occipital lobe. No significant interlobar differences were observed in AD thresholds. No significant differences were noted between within and outside epileptogenic zones. The distribution of ADs, remote spread was observed in all patients, reflecting fronto-parieto-temporal connections, as well as contiguous spread. The stimulation of premotor areas, the inferior parietal lobule, supplementary motor area, and basal temporal areas appeared to induce ADs in remote cortices. CONCLUSION: While no locational differences were observed in AD thresholds, each brain region showed a characteristic pattern for AD spread. Remote AD spread needs to be considered for safe functional mapping.

Location and Threshold of Electrical Cortical Stimulation for Functional Brain Mapping.

BACKGROUND AND OBJECTIVE: Although many studies have investigated functional localization by electrical stimulation, the threshold to identify each area remains controversial. The present study aimed to elucidate the threshold of a cortical stimulation for functional mapping. METHODS: We analyzed data from 17 patients with medically intractable epilepsy who underwent a 50-Hz electrical cortical stimulation for functional mapping between October 2013 and May 2017. The symptoms induced by the stimulation and the thresholds of the stimulation for these responses were evaluated. RESULTS: Motor responses were observed after the stimulation of the primary motor cortex, supplementary motor area, and frontal eye field, and sensory responses after the stimulation of the primary and secondary sensory cortex. Regarding negative responses, language impairment was observed after the stimulation of the anterior, posterior, and basal temporal language areas, negative motor responses after the stimulation of the premotor cortex, posterior parietal cortex, and the pre- supplementary motor area, and an impairment in spatial recognition after the stimulation of the right posterior parietal cortex. Negative or positive auditory symptoms were observed with the stimulation of the posterior superior temporal gyrus. The thresholds for positive phenomena were significantly lower than those for negative phenomena (Mann-Whitney U test, P < 0.01), and sensory responses were induced at significantly lower intensities than motor responses (P < 0.01). CONCLUSIONS: Positive and sensory effects are induced by lower intensities than negative and motor responses, respectively. The present results provide not only a practical guide for functional mapping, but also a hierarchal concept of processing in the brain.

Intracranial electrodes monitoring improves seizure control and complication outcomes for patients with temporal lobe epilepsy - A retrospective cohort study.

BACKGROUND: Anterior temporal lobectomy (ATL) is the standard surgical treatment for temporal lobe epilepsy (TLE), but patients may suffer from recurrent seizures post-surgery. Invasive electrical monitoring plays a critical role in precisely identifying the epileptic foci. This study aimed to evaluate and compare the benefits of long-term invasive electroencephalography (EEG) monitoring and two-stage surgery with the classical approach to examine their effect on post-surgical brain function and complications. MATERIALS AND METHODS: Patients with TLE (N = 198) who underwent epilepsy surgery were retrospectively evaluated. Diagnosis of TLE was confirmed based on clinical grounds (semiology), EEG findings, and magnetic resonance imaging (MRI). Long-term invasive video EEG was performed; epileptiform discharges were recorded. Patients underwent either classical ATL or modified two-step surgery with electrodes implantation. Histopathological examination was performed. The patients were followed up at 1, 3, and 5 years after surgery. RESULTS: Twenty-three and 175 patients underwent classical ATL and two-stage surgery, respectively. On histopathological examination, inflammation, hippocampal sclerosis, and cortical dysplasia were found to be the leading pathological causes of epileptic foci in both groups. MRI results were not consistent with the pathological findings. Grade II and III Engel scores were more frequent in the ATL group compared to two-stage surgery during follow-up. No postoperative complications were reported in two-stage surgery during follow-up, but one patient had mild hemiplegia in the ATL group. CONCLUSIONS: Preoperative invasive monitoring with long-term EEG helps locate the epileptic foci precisely. Postsurgical complications are rare compared to classical ATL, with better prognosis and seizure freedom after surgery.

[Surgical management of epilepsy]. / Prise en charge chirurgicale des épilepsies.

Epilepsy surgery raises hopes, but still remains reserved for a small number of cases of epilepsy resistant to medical treatments. It requires the involvement of multidisciplinary medical and allied health teams with expertise in this field. From the patient's admission through to their discharge, the nurse and the electroencephalogram technician have an essential role to play.

Fibrin sealant to prevent subdural electrode migration during intracranial electroencephalographic monitoring in a patient with a large arachnoid cyst.

Ensuring a stable position of intracranial electrode grids with good proximity to the cortical surface can be a technical challenge in patients with complex anomalous cerebral anatomy. This report illustrates the use of fibrin sealant to secure subdural electrodes to concave cortical surfaces during intracranial electroencephalographic monitoring for localization-related medically intractable epilepsy in a patient with a large arachnoid cyst.

Spatiotemporal dynamics and functional correlates of evoked neural oscillations with different spectral powers in human visual cortex.

OBJECTIVE: To investigate spatiotemporal characteristics and functional correlates of evoked oscillations (EOs) at different frequency bands in human visual cortex. METHODS: Flash visual evoked potentials (FVEPs) were recorded from 11 epilepsy patients with intracranial electrodes placed over the occipital and adjacent cortices. Spatiotemporal characteristics of spectral powers and correlation with various visual responses elicited by electrical cortical stimulations were analyzed in the same electrodes. RESULTS: High γ (60-150 Hz) EOs were first recorded in the cuneus and lingual gyri around the calcarine sulcus. Low γ (30-60 Hz) EOs appeared also in the mesial occipital cortex slightly later and lasted longer than high γ EGOs. In contrast, lower frequency (LF) <30 Hz EOs were recorded more diffusely from occipital surfaces with delayed onset and longer duration. High γ EOs were predominantly associated with simple form visual responses, whereas low γ and LF EOs were with intermediate form and LF EOs with complex form responses. CONCLUSIONS: FVEP spectral power analysis directly recorded from human visual cortex showed distinct spatiotemporal distributions in high and low γ, or LF bands that have different functional correlates. SIGNIFICANCE: Phase-locked EOs in these frequency bands may have special neuroanatomical and functional organization during early visual processing.