Editorial: Advances in Epilepsy Research: Exploring Biomarkers, Brain Stimulation, and Neurosurgical Interventions

Kazuki Sakakura¹Joel Oster^2*

• ¹Rush Medical College, Rush University, Chicago, Illinois, United States
• ²Tufts Medical Center, Boston, United States

Epilepsy remains one of the most prevalent and complex neurological disorders, affecting 1-2% people worldwide (Falco-Walter. 2020). Despite new advances in medications pharmacological treatments and numerous medications, a significant subsets of patients (approximately 35 %) remains medically refractory, necessitating innovative diagnostic and therapeutic approaches. ( Ben-Menachem E. 2014, Janson MT, Bainbridge JL 2021) Recent developments in biomarkers and neuroimaging provide a deeper understanding of Formatted: Not Highlight Commented [KS1]: Who is 1 st , 2 nd , and 3rd? And who is corresponding author? Formatted: Not Superscript/ Subscript Formatted: Not Superscript/ Subscript Formatted: Not Highlight Formatted: Indent: First line: 0 ch ictogenesis, seizure propagation, and surgical target identification. Electrophysiological biomarkers of epilepsy using electroencephalography (EEG) have been explored sinceed since the development around the discovery by Hans Berger in the1930s, with scalp EEG serving as a primary tool for seizure detection and analysis (Crone, 1998). Interictal and ictal discharges were observed subsequent to EEG's discovery and implantation. ByIn the 1990s, studiess tudies began reportingnoted that high-gamma oscillations observed through intracranial electrodes were associated with epileptogenicity (Chen et al. 2021, Zweiphenning, et al. 2022).Since the 2010s, phase-amplitude coupling, in which high-gamma oscillations are nested within slow waves, has been also recognized as a key biomarker of epilepsy (Motoi, et al. 2018, Sakakura, et al. 2024). Among the critical electrophysiological biomarkers of epilepsy, interictal spikes are particularly noteworthy (Asano, et al. 2009). Previous studies have suggested that the estimation of epileptogenic regions usingthe localizing value of interictal spikes and are is comparable to or even morecomplementary with ineffective than using evaluating high-gamma oscillations (Zweiphenning, et al. 2022). Within this context, Lu, et al. 2025 have recently highlighted an important finding using stereotactic-EEG (SEEG) in patients with mesial temporal lobe epilepsy. Their study focuses on morphological changes in preictal and interictal spike patterns, demonstrating that the emergence of hypersynchronous transients in clusters serves as a crucial indicator of transition from the interictal to the ictal state.In recent years, functional MRI (fMRI) has been increasingly utilized as a neuroimaging biomarker for epilepsy since. fMRI detects functional brain regions by measuring bloodoxygen-level-dependent signals and is widely used inmight be incrementally useful in the presurgical evaluation for epilepsy (Binder, et al. 2008). Beyond this application, more recent advancements have leveraged resting-state fMRI to analyze large-scale brain networks, allowing for a more comprehensive assessment of functional connectivity. across the brain (Bettus, et al. 2010). One of the key advantages of fMRI is its non-invasive nature, which allows for example study of comparisons between drug-resistant epilepsy patients and either healthy controls or drug-responsive epilepsy patients. This approach has facilitated investigations into the relationship between altered functional connectivity and cognitive impairment in drug-resistant epilepsy patients (Ibrahim, et al. 2014, Jiang, et al. 2018).Furthermore, some studies have suggested that functional connectivity assessments may serve as biomarkers for treatment resistance (Kay, et al. 2013). In this topic, Li, et al. 2024 have demonstrated changes in functional connectivity strength between the temporal lobe and the prefrontal cortex in drug-resistant epilepsy patients. Their findings suggest that the left caudate nucleus may serve as a potential target for improving both cognitive dysfunction and seizure control. Prior to surgical treatment for drug-resistant epilepsy, intracranial electrode placement is performed to identify both the seizure onset zone and critical functional areas. Intracranial electrodes are broadly categorized into subdural electrodes, which are placed on the cortical surface and which require a craniotomy, and SEEG, which does notwhich are placed into deep structures. In recent years, SEEG has been increasingly utilized due to its incrementally relatively lower decreasing invasiveness and increasing feasibility (Minotti, et al. 2018). SEEG along with cortical surface electrodes also a may allow for llows for electrode implantation in deep brain structures, necessitating high precision and safety in its application (Minotti, et al. 2018). Studies have reported that the use of computer-assisted planning during SEEG implantation improves both safety and gray matter sampling (Vakharia, et al. 2018). Furthermore, Dasgupta, et al. 2025 demonstrated that incorporating spatial constraints derived from previous SEEG trajectories enhances the accuracy and safety and speed of computer-assisted planning.Following intracranial electrode placement, in addition to seizure observation, electrical stimulation can provide critical preoperative information. One key application is functional mapping, which helps delineate motor and language areas before surgery (Baumgartner, et al. 2019). In this topic, Lu, et al. 2023 analyzed fMRI data from drug-resistant epilepsy patients following SEEG implantation and found that stimulation led to a decrease in functional connectivity strength between the frontal and temporal lobes, regions implicated in seizure onset. Their findings contribute to a deeper understanding of the pathophysiological networks underlying drug-resistant epilepsy.Surgical treatment is tailored to each patient's seizure type and clinical characteristics. When safe resection is feasible, resective surgery is considered a key intervention for achieving seizure freedom (Ryvlin, et al. 2014). However, if the seizure onset zone is not focal or if resection is expected to cause postoperative neurological deficits, alternative treatment options must be explored (Ryvlin, et al. 2014). Cottier, et al. 2024 conducted a systematic review and meta-analysis comparing resective and disconnective surgeries in patients with epileptic spasms. Their findings revealed that while only one-third or less of patients who underwent disconnective surgery achieved seizure freedom, two-thirds or more of those who underwent resective surgery became seizure-free.Among non-resective treatments, laser interstitial thermotherapy (LITT) has rapidly gained attention as a minimally invasive approach. Compared to resective surgery, LITT has been reported to potentially have a lower risk of cognitive impairment (Drane, et al. 2014). Using bibliometric analysis, Chen, et al. 2025 visualized the scientific progress and research trends in LITT, highlighting its expanding role in epilepsy treatment, although LITT may not be at present superior to seizure free outcomes from temporal lobectomy and LITT's authoritative outcome and indications are still evolving. Deep Brain Stimulation (DBS) has also gained increasing recognition as a non-resective approach. In the early 2000s, pilot trials targeting the anterior nucleus of the thalamus (ANT) were conducted in North America (Hodaie, et al. 2002, Kerrigan, et al. 2004). This led to the publication of the SANTE study in 2010, followed by FDA approval in 2012, after which ANT-DBS became more widely adopted in the United States (Fisher, et al. 2010). CM and pulvinar investiagions are currently evolving in treating Epilepsy. However, despite its growing acceptance, global implementation remains limited. Abzalova, et al. 2024 reported Kazakhstan's first case of ANT-DBS, underscoring its relatively lower adoption outside North America and Europe.The studies presented in this research topic highlight significant advancements in epilepsy research, encompassing biomarkers, neuroimaging techniques, surgical approaches, and neuromodulation interventions. We hope that readers will find this collection to be a valuable reference for both clinical practice and research.