Modulation of Interhemispheric Synchronization and Cortical Activity in Healthy Subjects by High-Definition Theta-Burst Electrical Stimulation.

Background: Various forms of theta-burst stimulation (TBS) such as intermittent TBS (iTBS) and continuous TBS (cTBS) have been introduced as novel facilitation/suppression schemes during repetitive transcranial magnetic stimulation (rTMS), demonstrating a better efficacy than conventional paradigms. Herein, we extended the rTMS-TBS schemes to electrical stimulation of high-definition montage (HD-TBS) and investigated its neural effects on the human brain. Methods: In a within-subject design, fifteen right-handed healthy adults randomly participated in 10 min and 2 mA HD-TBS sessions: unilateral (Uni)-iTBS, bilateral (Bi)-cTBS/iTBS, and sham stimulation over primary motor cortex regions. A 20-channel near-infrared spectroscopy (NIRS) system was covered on the bilateral prefrontal cortex (PFC), sensory motor cortex (SMC), and parietal lobe (PL) for observing cerebral hemodynamic responses in the resting-state and during fast finger-tapping tasks at pre-, during, and poststimulation. Interhemispheric correlation coefficient (IHCC) and wavelet phase coherence (WPCO) from resting-state NIRS and concentration of oxyhemoglobin during fast finger-tapping tasks were explored to reflect the symmetry between the two hemispheres and cortical activity, respectively. Results: The IHCC and WPCO of NIRS data in the SMC region under Bi-cTBS/iTBS showed relatively small values at low-frequency bands III (0.06-0.15 Hz) and IV (0.02-0.06), indicating a significant desynchronization in both time and frequency domains. In addition, the SMC activation induced by fast finger-tapping exercise was significantly greater during Uni-iTBS as well as during and post Bi-cTBS/iTBS sessions. Conclusions: It appears that a 10 min and 2 mA Bi-cTBS/iTBS applied over two hemispheres within the primary motor cortex region could effectively modulate the interhemispheric synchronization and cortical activation in the SMC of healthy subjects. Our study demonstrated that bilateral HD-TBS approaches is an effective noninvasive brain stimulation scheme which could be a novel therapeutic for inducing effects of neuromodulation on various neurological disorders caused by ischemic stroke or traumatic brain injuries.

Real-Time Internet of Medical Things System for Detecting Blood Leakage during Hemodialysis Using a Novel Multiple Concentric Ring Sensor.

Venous needle dislodgement (VND) is a major healthcare safety concern in patients undergoing hemodialysis. Although VND is uncommon, it can be life-threatening. The main objective of this study was to implement a real-time multi-bed monitoring system for VND by combining a novel leakage-detection device and IoMT (Internet of Medical Things) technology. The core of the system, the Acusense IoMT platform, consisted of a novel leakage-detection patch comprised of multiple concentric rings to detect blood leakage and quantify the leaked volume. The performance of the leakage-detection system was evaluated on a prosthetic arm and clinical study. Patients with a high risk of blood leakage were recruited as candidates. The system was set up in a hospital, and the subjects were monitored for 2 months. During the pre-clinical simulation experiment, the system could detect blood leakage volumes from 0.3 to 0.9 mL. During the test of the IoMT system, the overall success rate of tests was 100%, with no lost data packets. A total of 701 dialysis sessions were analyzed, and the accuracy and sensitivity were 99.7% and 90.9%, respectively. Evaluation questionnaires showed that the use of the system after training changed attitudes and reduced worry of the nursing staff. Our results show the feasibility of using a novel detector combined with an IoMT system to automatically monitor multi-bed blood leakage. The innovative concentric-circle design could more precisely control the warning blood-leakage threshold in any direction to achieve clinical cost-effectiveness. The system reduced the load on medical staff and improved patient safety. In the future, it could also be applied to home hemodialysis for telemedicine during the era of COVID-19.

Hemodynamics and Tissue Optical Properties in Bimodal Infarctions Induced by Middle Cerebral Artery Occlusion.

Various infarct sizes induced by middle cerebral artery occlusion (MCAO) generate inconsistent outcomes for stroke preclinical study. Monitoring cerebral hemodynamics may help to verify the outcome of MCAO. The aim of this study was to investigate the changes in brain tissue optical properties by frequency-domain near-infrared spectroscopy (FD-NIRS), and establish the relationship between cerebral hemodynamics and infarct variation in MCAO model. The rats were undergone transient MCAO using intraluminal filament. The optical properties and hemodynamics were measured by placing the FD-NIRS probes on the scalp of the head before, during, and at various time-courses after MCAO. Bimodal infarction severities were observed after the same 90-min MCAO condition. Significant decreases in concentrations of oxygenated hemoglobin ([HbO]) and total hemoglobin ([HbT]), tissue oxygenation saturation (StO2), absorption coefficient (µa) at 830 nm, and reduced scattering coefficient (µs') at both 690 and 830 nm were detected during the occlusion in the severe infarction but not the mild one. Of note, the significant increases in [HbO], [HbT], StO2, and µa at both 690 and 830 nm were found on day 3; and increases in µs' at both 690 and 830 nm were found on day 2 and day 3 after MCAO, respectively. The interhemispheric correlation coefficient (IHCC) was computed from low-frequency hemodynamic oscillation of both hemispheres. Lower IHCCs standing for interhemispheric desynchronizations were found in both mild and severe infarction during occlusion, and only in severe infarction after reperfusion. Our finding supports that sequential FD-NIRS parameters may associated with the severity of the infarction in MCAO model, and the consequent pathologies such as vascular dysfunction and brain edema. Further study is required to validate the potential use of FD-NIRS as a monitor for MCAO verification.

Real-world evidence on the safety and effectiveness of fingolimod in patients with multiple sclerosis from Taiwan.

BACKGROUND/PURPOSE: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. METHODS: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). RESULTS: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 103/uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353. CONCLUSION: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan.

Innovative Head-Mounted System Based on Inertial Sensors and Magnetometer for Detecting Falling Movements.

This work presents a fall detection system that is worn on the head, where the acceleration and posture are stable such that everyday movement can be identified without disturbing the wearer. Falling movements are recognized by comparing the acceleration and orientation of a wearer's head using prespecified thresholds. The proposed system consists of a triaxial accelerometer, gyroscope, and magnetometer; as such, a Madgwick's filter is adopted to improve the accuracy of the estimation of orientation. Moreover, with its integrated Wi-Fi module, the proposed system can notify an emergency contact in a timely manner to provide help for the falling person. Based on experimental results concerning falling movements and activities of daily living, the proposed system achieved a sensitivity of 96.67% in fall detection, with a specificity of 98.27%, and, therefore, is suitable for detecting falling movements in daily life.

Cortical Excitability by Transcranial Magnetic Stimulation as Biomarkers for Seizure Controllability in Temporal Lobe Epilepsy.

OBJECTIVE: To investigate whether indicators of cortical excitability are good biomarkers of seizure controllability in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Three groups of subjects were recruited: those with poorly controlled (PC) TLE (N = 41), well-controlled (WC) TLE (N = 71), and healthy controls (N = 44). Short- and long-latency recovery curves were obtained by paired-pulse transcranial magnetic stimulation. Linear mixed effect models were used to study the effects of group, interstimulus interval (ISI), and antiepileptic drugs on long-interval intracortical inhibition (LICI) and short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). RESULTS: The mixed effect model that did not incorporate antiepileptic drugs showed that group and ISI were significant factors for LICI and SICI/ICF. LICI in the healthy control group was greater than in the two epilepsy groups, and the difference was significant at ISIs of 50, 150, and 200 msec. In contrast, SICI/ICF in the PC group was greater than in the healthy control and WC groups, and the difference was significant at an ISI of 15 msec. However, due to large variance, it was difficult to identify a cutoff value with both good sensitivity and good specificity. Incorporating the information of antiepileptic drugs to the mixed effect model did not change the overall results. CONCLUSIONS: Although LICI and SICI/ICF parameters were significantly different at the group level, they may not be suitable biomarkers for the controllability of TLE at the subject level.

Methodological standards for in vitro models of epilepsy and epileptic seizures. A TASK1-WG4 report of the AES/ILAE Translational Task Force of the ILAE.

In vitro preparations are a powerful tool to explore the mechanisms and processes underlying epileptogenesis and ictogenesis. In this review, we critically review the numerous in vitro methodologies utilized in epilepsy research. We provide support for the inclusion of detailed descriptions of techniques, including often ignored parameters with unpredictable yet significant effects on study reproducibility and outcomes. In addition, we explore how recent developments in brain slice preparation relate to their use as models of epileptic activity.

Modulating the interference effect on spatial working memory by applying transcranial direct current stimulation over the right dorsolateral prefrontal cortex.

Spatial working memory (SWM) is the ability to temporarily store and manipulate spatial information. It has a limited capacity and is quite vulnerable to interference. Dorsolateral prefrontal cortex (DLPFC) has been shown to be a part of the SWM network but its specific functional role still remains unknown. Here we applied transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique that provides polarity-specific stimulation over the targeted region, to investigate the specific role of the right DLPFC in resolving interference in SWM. A forward- and backward-recall computerized Corsi Block Tapping task (CBT), both with and without a concurrent motor interference task (the modified Luria manual sequencing task) was used to measure SWM capacity and reaction time. The results showed that motor interference impeded accuracy and prolonged reaction time in forward and backward recall for SWM. Anodal tDCS over right DLPFC yielded the tendency to shorten participants' reaction time in the conditions with interference (forward with interference, and backward with interference). Most importantly, anodal tDCS significantly improved participants' SWM span when cognitive demand was the highest (the "backward-recall with motor interference" condition). These results suggest that (1) the right DLPFC plays a crucial role in dealing with the cross-domain motor interference for spatial working memory and (2) the anodal tDCS over right DLPFC improved SWM capacity particularly when task difficulty demands more complex mental manipulations that could be due to the facilitatory effect of anodal tDCS which enhanced the DLPFC function within central executive system at the top-down attentional level.

Temporal course of streptozotocin-induced diabetic polyneuropathy in rats.

The temporal course of diabetic polyneuropathy in a rat model plays a critical role in studies on diabetic polyneuropathy treatment. In this study, the temporal course of neuropathic symptoms was investigated in diabetic rats induced by streptozotocin and evaluated by nerve conduction velocity and behavioral assays, including the von Frey test for mechanical allodynia and the hot plate test for hyperalgesia. The results revealed that both mechanical allodynia and heat hyperalgesia started on the 2nd week, while nerve conduction velocity significantly decreased from the 1st week. In addition, the severity of allodynia did not change after the 3rd week. Hyperalgesia and nerve conduction velocity progressively aggravated even to the 8th week. Transmission electron microscopy showed that loss of unmyelinated axons, loosening of the myelin structure, and thickening of the perineurium layer were visible from the 4th week and worsened on the 8th week. Differences in the temporal course of neuropathic symptoms are discussed.

Diffusion-weighted imaging as an aid in the diagnosis of the etiology of medial longitudinal fasciculus syndrome.

PURPOSE: Internuclear ophthalmoplegia is caused by a lesion; stroke, multiple sclerosis, brain metastases, or trauma may produce lesions of the medial longitudinal fasciculus (MLF). Imaging techniques, such as DWI, can help identify the site of the lesion in order to speed diagnosis and lead to appropriate treatment. METHODS: Over an 8-month period, eight consecutive patients with suspected MLF syndrome (most secondary to ischemic stroke) underwent MRI examinations, including DWI sequencing, at an academic center in Taiwan. RESULTS: In all eight patients, abnormal high-signal lesions were found close to the floor of the fourth ventricle on the dorsal side of the pons. A neuroanatomical comparison showed that the location of the lesions was identical to the anatomical position of the MLF. CONCLUSION: Using DWI, good clinico-radiological correlation was found in all eight ischemic stroke patients diagnosed with MLF syndrome. DWI may broaden the application of MRI in the diagnosis of MLF syndrome.

Using a discrete preisach model for hysteresis in ankle joint passive moment.

The steady-state passive joint moment was considered as a nonlinear elasticity in the past. However, we found that it was path dependent and the estimation error could be large if the commonly used path-independent functions were adopted. The aim of this study was to develop a model to describe the movement history-dependent passive moment in the steady state. The steady-state passive ankle moments of the rabbit were measured by a series of ramp-and-hold angle changes (stairway angle trajectory). A customized discrete Preisach model was constructed and a commonly adopted double-exponential function was also implemented. Two sets of data with different angle paths (major loop and inward loop trajectories) were acquired for model validation. The performance of the two models was compared. The results showed that the proposed model could accurately estimate the steady-state passive moment for both sets of validation data. The estimated error of the proposed model was approximately 50% smaller than that of the double-exponential function approach. It is expected that this new approach, by reducing the error of estimating passive joint moment, may contribute to the active control of joint moments.

Charge-mode Neural Stimulator with a Capacitor-reuse Residual Charge Detector and Active Charge Balancing for Epileptic Seizure Suppression.

This study proposes a charge-mode neural stimulator for electrical stimulation systems that utilizes a capacitor-reuse technique with a residual charge detector and achieves active charge balancing simultaneously. The design is mainly used for epilepsy suppression systems to achieve real-time symptom relief during seizures. A charge-mode stimulator is adopted in consideration of the complexity of circuit design, the high voltage tolerance of transistors, and system integration requirements in the future. The residual charge detector allows users to understand the current stimulus situation, enabling them to make optimal adjustments to the stimulation parameters. On the basis of the information on actual stimulation charge, active charge balancing can effectively prevent the accumulation of mismatched charges on electrode impedance. The capacitor- and phase-reuse techniques help realize high integration of the overall stimulator circuit in consideration of the commonality of the use of a capacitor and charging/discharging phase in the stimulation circuit and charge detector. The proposed charge-mode neural stimulator is implemented in a TSMC 0.18 µm 1P6M CMOS process with a core area of 0.2127 mm2. Measurement results demonstrate the accuracy of the stimulation's functionality and the programmable stimulus parameters. The effectiveness of the proposed charge-mode neural stimulator for epileptic seizure suppression is verified through animal experiments.

The distinct and potentially conflicting effects of tDCS and tRNS on brain connectivity, cortical inhibition, and visuospatial memory.

Noninvasive brain stimulation (NIBS) techniques, including transcranial direct current stimulation (tDCS) and transcranial random noise stimulation (tRNS), are emerging as promising tools for enhancing cognitive functions by modulating brain activity and enhancing cognitive functions. Despite their potential, the specific and combined effects of tDCS and tRNS on brain functions, especially regarding functional connectivity, cortical inhibition, and memory performance, are not well-understood. This study aims to explore the distinct and combined impacts of tDCS and tRNS on these neural and cognitive parameters. Using a within-subject design, ten participants underwent four stimulation conditions: sham, tDCS, tRNS, and combined tDCS + tRNS. We assessed the impact on resting-state functional connectivity, cortical inhibition via Cortical Silent Period (CSP), and visuospatial memory performance using the Corsi Block-tapping Test (CBT). Our results indicate that while tDCS appears to induce brain lateralization, tRNS has more generalized and dispersive effects. Interestingly, the combined application of tDCS and tRNS did not amplify these effects but rather suggested a non-synergistic interaction, possibly due to divergent mechanistic pathways, as observed across fMRI, CSP, and CBT measures. These findings illuminate the complex interplay between tDCS and tRNS, highlighting their non-additive effects when used concurrently and underscoring the necessity for further research to optimize their application for cognitive enhancement.

Model-based spike detection of epileptic EEG data.

Accurate automatic spike detection is highly beneficial to clinical assessment of epileptic electroencephalogram (EEG) data. In this paper, a new two-stage approach is proposed for epileptic spike detection. First, the k-point nonlinear energy operator (k-NEO) is adopted to detect all possible spike candidates, then a newly proposed spike model with slow wave features is applied to these candidates for spike classification. Experimental results show that the proposed system, using the AdaBoost classifier, outperforms the conventional method in both two- and three-class EEG pattern classification problems. The proposed system not only achieves better accuracy for spike detection, but also provides new ability to differentiate between spikes and spikes with slow waves. Though spikes with slow waves occur frequently in epileptic EEGs, they are not used in conventional spike detection. Identifying spikes with slow waves allows the proposed system to have better capability for assisting clinical neurologists in routine EEG examinations and epileptic diagnosis.

Epidermoid cyst presenting as isolated trigeminal neuralgia - two case reports.

PURPOSE: Symptomatic TN accounts for up to 15% of all TN. Though there are many established "red flag" signs, it is still sometimes difficult to sift symptomatic from classic TN. We herein report two cases of isolated TN with normal neurologic examinations and then tissue proved as epidermoid cyst. CASE 1: A 17-year-old girl presented with paroxysmal intense pain mixed dull background pain at right mandibular region for one month. The blink reflex demonstrated brainstem lesion and brain magnetic resonance imaging (MRI) revealed a huge lobulated tumor in right cerebellopontine angle (CPA) with obvious brainstem compression. Her right facial pain was nearly completely disappeared postoperatively. CASE 2: The 48-year-old woman had chronic paroxysmal electric-like and burning pain in left V3 region for more than 5 years. Because of refractory pain, brain MRI was arranged and showed a non-enhancing cystic lesion at left CPA. Post operative complications occurred as left multiple lower cranial nerve palsies and Horner syndrome, and truncal ataxia. Her facial pain was completely free after 1 month follow up. CONCLUSION: In the first patient, teenage onset, abnormal trigeminal reflex, and early developing background pain struck us directly to symptomatic TN. In the second case, we suspected symptomatic TN with uncertainty before image study. TN could be the isolated initial symptom of CPA epidermoid cysts. In consideration about pretty high prevalence of symptomatic TN, physicians should be more alert and straightforward arrange neuroimage when facing TN patients with atypical presentation.

Nerve excitability test and lead toxicity: a case-control study.

BACKGROUND: Although conventional electrophysiological parameters have been proposed as clinical indicators for monitoring lead neuropathies, their correlations with blood lead level are weak. In this study, we investigated the applicability of nerve excitability tests (NETs) to evaluate lead intoxication. METHODS: Fourteen workers who were exposed to lead with an elevated blood level ranging from 17.8 to 64.9 µg/dL and 20 healthy controls with similar ages and body heights were enrolled. Both workers and controls underwent nerve conduction studies (NCSs), motor evoked potentials (MEPs) with transcranial magnetic stimulation (TMS), and NETs. RESULTS: NCSs showed prolonged distal latencies and decreased motor nerve conduction velocity of median nerves in the workers but without significant correlation to blood lead level (BLL). Significantly prolonged MEP latency was observed in the workers (+ 6 ms). NETs demonstrated hyperpolarized resting membrane potentials in stimulus-response curves and changes in the property of potassium channels under a hyperpolarized current in threshold electrotonus, implying that lead hyperpolarized nerves by interfering with potassium channels. NETs also showed a better correlation with BLL than conventional electrophysiological parameters. CONCLUSIONS: Axonal hyperpolarization and central conduction delay are more apparently reflecting elevated BLL than NCS. NET may have the potential for early detection of lead neuropathy.

New biophysical rate-based modeling of long-term plasticity in mean-field neuronal population models.

The formation of customized neural networks as the basis of brain functions such as receptive field selectivity, learning or memory depends heavily on the long-term plasticity of synaptic connections. However, the current mean-field population models commonly used to simulate large-scale neural network dynamics lack explicit links to the underlying cellular mechanisms of long-term plasticity. In this study, we developed a new mean-field population model, the plastic density-based neural mass model (pdNMM), by incorporating a newly developed rate-based plasticity model based on the calcium control hypothesis into an existing density-based neural mass model. Derivation of the plasticity model was carried out using population density methods. Our results showed that the synaptic plasticity represented by the resulting rate-based plasticity model exhibited Bienenstock-Cooper-Munro-like learning rules. Furthermore, we demonstrated that the pdNMM accurately reproduced previous experimental observations of long-term plasticity, including characteristics of Hebbian plasticity such as longevity, associativity and input specificity, on hippocampal slices, and the formation of receptive field selectivity in the visual cortex. In conclusion, the pdNMM is a novel approach that can confer long-term plasticity to conventional mean-field neuronal population models.

The influences of inter-trial interval on the thermal and thermal pain thresholds in quantitative sensory testing.

PURPOSE: Thermal threshold and thermal pain threshold determinations are part of quantitative sensory tests. Usually the average of many repeated trials is defined as the threshold. The inter-trial interval (ITI) may have an effect on the later trials. The main purpose of this study was to investigate the influence of ITI on the test results. METHODS: Forty-two healthy subjects were recruited. The limit method was adopted. Each subject received 4 sessions of testing, with one ITI equal to 10, 20, 40 and 60 seconds, respectively. In each session, all four modalities (warm and cold thresholds and cold and hot pain thresholds) were performed. Thermal thresholds were the averages of four trials and thermal pain thresholds were the averages of three trials. The ITI order and the modality order were pseudo-randomized. Analyses of variance were utilized to test the influence of ITI, the modality order and the trial order. RESULTS: The results implied that the test results by the limit method are independent of ITI in the range of 10 to 60 seconds, but the results may not be the true thresholds. CONCLUSION: The results showed that while ITI and the modality order did not have significant effects on the test results, the trial order did have effects on the results of all modalities.

The Proper Use and Reporting of Survival Analysis and Cox Regression.

BACKGROUND: Survival analyses are heavily used to analyze data in which the time to event is of interest. The purpose of this paper is to introduce some fundamental concepts for survival analyses in medical studies. METHODS: We comprehensively review current survival methodologies, such as the nonparametric Kaplan-Meier method used to estimate survival probability, the log-rank test, one of the most popular tests for comparing survival curves, and the Cox proportional hazard model, which is used for building the relationship between survival time and specific risk factors. More advanced methods, such as time-dependent receiver operating characteristic, restricted mean survival time, and time-dependent covariates are also introduced. RESULTS: This tutorial is aimed toward covering the basics of survival analysis. We used a neurosurgical case series of surgically treated brain metastases from non-small cell lung cancer patients as an example. The survival time was defined from the date of craniotomy to the date of patient death. CONCLUSIONS: This work is an attempt to encourage more investigators/medical practitioners to use survival analyses appropriately in medical research. We highlight some statistical issues, make recommendations, and provide more advanced survival modeling in this aspect.

Using Constrained Square-Root Cubature Kalman Filter for Quantifying the Severity of Epileptic Activities in Mice.

(1) Background: Quantification of severity of epileptic activities, especially during electrical stimulation, is an unmet need for seizure control and evaluation of therapeutic efficacy. In this study, a parameter ratio derived from constrained square-root cubature Kalman filter (CSCKF) was formulated to quantify the excitability of local neural network and compared with three commonly used indicators, namely, band power, Teager energy operator, and sample entropy, to objectively determine their effectiveness in quantifying the severity of epileptiform discharges in mice. (2) Methods: A set of one normal and four types of epileptic EEGs was generated by a mathematical model. EEG data of epileptiform discharges during two types of electrical stimulation were recorded in 20 mice. Then, EEG segments of 5 s in length before, during and after the real and sham stimulation were collected. Both simulated and experimental data were used to compare the consistency and differences among the performance indicators. (3) Results: For the experimental data, the results of the four indicators were inconsistent during both types of electrical stimulation, although there was a trend that seizure severity changed with the indicators. For the simulated data, when the simulated EEG segments were used, the results of all four indicators were similar; however, this trend did not match the trend of excitability of the model network. In the model output which retained the DC component, except for the CSCKF parameter ratio, the results of the other three indicators were almost identical to those using the simulated EEG. For CSCKF, the parameter ratio faithfully reflected the excitability of the neural network. (4) Conclusion: For common EEG, CSCKF did not outperform other commonly used performance indicators. However, for EEG with a preserved DC component, CSCKF had the potential to quantify the excitability of the neural network and the associated severity of epileptiform discharges.