Stereotactic electroencephalography (SEEG): A Modern Approach to Epilepsy and Neuroscience Research

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Written by Ayush Halder

Edited by Fahad Hassan Shah

1. Introduction

Epilepsy is a neurological disease characterized by recurrent, unprovoked, abnormal electrical brain activity causing seizures. These abnormal brain waves can arise from a region on one side of the brain, simultaneously from both sides, or spread from one side and engage both brain hemispheres.

While its clinical presentation is heterogeneous, symptoms such as motor phenomena observed in convulsions can be readily visible, or they may be hidden within the brain, as seen in sensory, cognitive, emotional, or autonomic alterations. During such episodes, consciousness may be intact or lost. The durations can range from brief lapses in awareness to prolonged convulsions, known as status epilepticus (Fisher et al., 2017).

Epilepsy is one of the most common and serious neurological conditions, affecting around 50 million people globally, making it the most widespread chronic brain disorder. Despite being highly treatable, with the possibility of up to 70% of patients achieving seizure control through appropriate medical interventions, epilepsy remains stigmatized and underdiagnosed in many parts of the world (World Health Organization, 2019). Moreover, about 20-40% of people with epilepsy are classified as drug-resistant, meaning their seizures do not respond adequately to antiseizure medications (Kalilani et al., 2018). In such complex cases, advanced diagnostic tools like stereotactic electroencephalography (SEEG) can play a pivotal role in precisely localizing the seizure zones in the brain and help guide potential surgical interventions, such as resective surgery, ablation, or neurostimulation, to control seizures.

Context and the importance of better epilepsy monitoring methods such as SEEG

1. Why and when are invasive EEG monitoring techniques needed?

Most epileptic seizures originate in the cortex, which lies close to the surface of the brain (Figure 1). In such cases, scalp electroencephalography (EEG) is typically sufficient for detecting abnormal electrical activity due to its ability to record surface-level signals. However, not all seizure activity is so easily captured. The seizure onset zone can often be located in deep brain structures (subcortical) such as the hippocampus, amygdala, thalamus, or basal ganglia (Zangiabadi et al., 2019). These regions are more electrically shielded due to their signal attenuation before reaching the scalp, distortions by nearby tissues, etc., (Subramanian et al., 2025).

Figure 1

Image depicting the areas of the cortex where seizures may occur and their corresponding clinical presentation

Note. Copyright from: Chapter 2, The Anatomical Basis of Seizures. Epilepsy [internet] Czuczwar SJ, editor. Brisbane (AU): Exon Publications; 2022 Apr 2. Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0).

If the seizures are drug-resistant, the diseased part of the brain may need to be cut out, either by ablation or resection. In such surgical cases, it is crucial to be as precise with the resectable area as possible to ensure the patient does not lose brain function of normal tissues.

A scalp EEG records electrical activity from the brain via electrodes placed on the scalp. This is good for detecting discharges produced near the skull, i.e., at the cortex. It is the best at recording any electrical activity at the exact time the epileptiform discharge occurs (good temporal resolution). But when it comes to localizing activity, especially from deep brain structures, there is poor spatial resolution. Usually, MRIs have better spatial resolution and a poor temporal resolution; hence, MRIs are always complemented with an EEG (Janiukstyte et al., 2023; Lüders et al., 2006; Subramanian et al., 2025).

With scalp EEG, this diagnostic limitation presents a major obstacle in identifying the precise location of the seizure, which is vital for the localization of epileptiform discharges and a successful surgical intervention.

2. SEEG’s role

When non-invasive methods fail to provide definitive data, stereotactic electroencephalography (SEEG) offers an effective alternative. By implanting depth electrodes directly into targeted brain regions, SEEG allows for three-dimensional neural activity mapping, including areas otherwise inaccessible by surface techniques. This invasive approach is particularly effective in evaluating patients with seizures originating from subcortical regions, which scalp EEG inaccurately interprets.

Key objectives of this article

This article will focus on stereotactic electroencephalography (SEEG). It will cover the basics of the technical aspects of how an encephalogram is created, the clinical applications of SEEG, its benefits and limitations, and consider what the future may hold for this important tool in epilepsy diagnosis and brain research.

2. What is SEEG

Stereotactic EEG (SEEG) is an advanced, minimally invasive neurophysiological technique that records electrical activity within the brain. Using a stereotactic procedure, tiny electrodes are placed with fine precision within the brain matter through tiny ‘burr’ holes in the skull, and these electrodes are used to capture a 3D map of epileptiform activity from any given region within the brain (Figure 2).

Figure 2

Basic illustration of SEEG electrodes implanted through burr holes in the skull. These electrodes can pass at various angles through both gray and white matter.

Note. Copyright from: Electrical Stimulation Mapping of Brain Function: A Comparison of Subdural Electrodes and Stereo-EEG. Front. Hum. Neurosci. Grande et al. Creative Commons Attribution 4.0 International (changes: only image cropping)

3. Indications and Applications of SEEG

Primary Clinical Use: Epilepsy Diagnosis & Pre-Surgical Planning

The usual diagnostic flow of any suspected seizures includes (1) a detailed clinical history, (2) a clear brain image, such as an MRI, and (3) an electrographic brainwave test → scalp EEG or a video EEG (either as an outpatient procedure lasting a few hours or an entire 7-day inpatient or home monitoring). Based on some studies, over 97% to 99% of first seizure events can be observed if continuous VEEG is monitored for 3-5 days (Foong & Seneviratne, 2016; Klein et al., 2021). 

In cases where the EEGs (including video EEGs) show an inconclusive or negative report, SEEG can successfully localize seizure activity when scalp EEG plus MRI falls short in finding the seizure foci in the brain (Snehal et al., 2022; What We’ve Learned From Our First 1,000 Cases of SEEG Evaluation, n.d.). 

However, the primary use of SEEG is mainly to perform the presurgical workup of drug-resistant epilepsy (DRE) to delineate the diseased brain matter precisely if the MRI with the scalp EEG is inconclusive of the epileptogenic zone (EZ) or if the EZ is very close to brain areas that have critical functions (Peltola et al., 2023). Once the EZ is within sight, the lesion can be surgically removed using ablation (radio frequency or laser) or surgical resection, or implants can be placed to sever the connection between the EZ and the rest of the brain, called neuromodulation (stereoelectroencephalography (SEEG) | neurological surgery | University of Pittsburgh, n.d.).

SEEG Beyond Epilepsy: Theorized and Current Uses

While originally developed for epilepsy, SEEG can help map real-time brain activity with the benefit of good anatomical resolution. This offers windows of opportunity to look deeper into the brain to understand the neuronal pathways and use them for patient care (Delgado-Garcia & Frauscher, 2022; Scullen et al., 2021; Wang et al., 2024).

1) Theorized Applications:

• Neuropsychiatric Research: SEEG could help uncover the anomalous brain network activity in disorders like schizophrenia and addiction disorders by mapping out unique neural circuits, which can vary from person to person. This can help individualize the treatment on an as-needed basis.

• Targeting for Neuromodulation: Similar to implant placement in epilepsy, SEEG may help identify precise stimulation targets for conditions like Parkinson’s, essential tremor, and treatment-resistant depression.

• Mapping circuits and understanding Brain Function: SEEG can map out how various brain regions interact during complex cognitive tasks, like emotional processing and problem-solving, and thus, identify disruptions in neurological diseases.

• Brain-Computer Interfaces (BCIs): SEEG could play a role in developing BCIs by providing precise neural signals for controlling external devices, such as prosthetics.

2) Current Non-Epilepsy Uses:

Work on SEEG in research is currently limited to its use in epileptic patients.

• Research from Epilepsy Data: SEEG datasets can be reused from epilepsy candidates to study 1) brain behavior, cognitive tasks, and functional mapping, which includes the well-known use of ESM (electrical stimulation mapping), where minuscule amounts of electrical currents are conducted through the electrodes to observe a response and map out the functional regions of the brain (Grande et al., 2020). 2) Get detailed information on sleep waves from deeper regions of the brain as part of a sleep study. 

4. Technical Aspects of SEEG

Pre-Surgical Planning

Pre-surgical planning is a cornerstone of SEEG and begins with the integration of high-resolution anatomical imaging (MRI and CT) and functional imaging, such as PET, SPECT, or diffusion tensor imaging (DTI) with EEG or magnetoencephalography (MEG) scans. These help localize the epileptogenic zone (EZ) and provide details on nearby normal and critical functioning areas of the brain. This gives the clearest picture possible of the anatomical and electrical scenario of the patient, referred to as ‘Anatomoelectroclinical correlations’ (AEC) hypotheses.

A multidisciplinary team—including epileptologists, radiologists, neurosurgeons, and technicians—collaborates with the advanced machinery to generate patient-specific brain images and plan electrode trajectories that will ultimately sample cortical and subcortical areas suspected of seizure initiation and/or propagation.

Electrode Implantation Procedure

To prepare the surgical site, scalp hair may be clipped or left intact and made sterile, but never shaved, to avoid micro-abrasion or folliculitis and the risk of skin infection. Prophylactic antibiotics are given according to usual surgical protocols. The patient is put under general anesthesia.

The anatomical images of the patient are transferred to stereotactic neuronavigation software, which helps plan the trajectories of the tiny electrodes.

SEEG implantation is performed using either a frame-based stereotactic system (e.g., Leksell frame by Elekta) or frameless, robot-assisted systems like ROSA® (figure 3). The procedure involves drilling small burr holes (typically 2–3 mm) and inserting multiple depth electrodes guided by preoperative trajectory maps.

Figure 3

ROSA: Robotic Stereotactic Arm for SEEG placement

Note. Courtesy: Dr. Jaivir S. Rathore, MD, FAES, FAAN USA

If possible or needed, intraoperative imaging using MRI or CT may be required if there is suspicion of altered trajectory or to make minor adjustments.

The electrodes are secured with anchoring bolts to the skull, and a postoperative CT or MRI is used to verify their location (figure 4). Frame-based systems offer better precision but are more time-consuming. Robotic systems enhance flexibility and speed and are becoming standard in many epilepsy centers.

Figure 4

MRI Brain with SEEG depth electrodes (red arrows)

Note. Courtesy: Dr. Jaivir S. Rathore, MD, FAES, FAAN USA

The electrodes are made of non-ferromagnetic material like platinum-iridium (standard) or any proprietary alloy that is unaffected by MRI. (Bezchlibnyk et al., 2024). Electrode design differs; some may allow for the simultaneous recording of electrical signals and single-cell discharges as an added benefit. 

Safety: The trajectory of electrode insertion is predetermined by vascular imaging, such as MR/CT angiography, to create minimal vasculature injury.

Once the procedure is completed, the external segments of the electrodes are bandaged to prevent any leaks and avoid contamination. Scans are done post-operatively to look at the positioning of electrodes and observe any local brain swelling or bleeds (hematoma) around the surgical sites. (Alomar et al., 2016; Guénot et al., 2018; Ryvlin, 2025; Zhong et al., 2025)

Data Acquisition & Analysis

Once implanted, electrodes capture high-resolution signals from both grey and white matter structures at multiple depths. These electrical waves are continuously recorded in a controlled hospital setting, often over several days. After running multiple algorithms using special software, the signals are processed, analyzed, and presented to the viewer.

Steps:

1. Capturing data: SEEG systems record intracranial signals at high sampling rates (often ≥1 kilohertz) to reliably capture any epileptiform discharges during seizures and between such episodes.

2. Preprocessing & artifact removal: Raw recordings are filtered (to focus on the seizure-relevant frequencies), and notch filtering (to eliminate power line interference; 50 Hz in the USA and 60 Hz in Europe) is done. Artifacts caused by the movement of muscles or other physiological noise are similarly removed.

3. Processing, analysis, and interpretation: After removal of noise and artifacts, the signals are provided and visualized as an EEG waveform. Some useful software (adaptable for SEEG) for analysis includes: 

   1. MATLAB-based: EEGLAB, Brainstorm, and FieldTrip.

   2. Python-Based: MNE-Python.

   3. Other standalone platforms: CURRY Neuro Imaging Suite.

5. Challenges and Limitations of SEEG

While SEEG offers many benefits, its invasive nature presents surgical safety concerns and interpretative and ethical limitations that require careful consideration.

Surgical complications

Being an invasive procedure, the insertion of multiple tiny electrodes through the scalp, bony skull, meninges, and into brain tissue presents some risks. The most commonly reported complications include (Mullin et al., 2016):

• Bleeding: During the procedure, if any blood vessel is nicked, bleeding can occur, and because depth electrodes are being inserted within the brain matter, the most important risks to consider are damage to cerebral vessels and cerebral edema. 

• Infections: Infections can range from local superficial scalp infections to deadly meningitis or brain abscesses.

• Hardware-related complications include improper positioning of electrodes requiring reinsertion, electrode dislodgement or damage to the delicate electrodes intraoperatively, or malfunctioning. The worst-case scenario would be an electrode fracture within the brain, which would require a craniotomy to be removed. 

• Interpretation complexities: Interpreting SEEG is more complex than scalp EEG due to a comparatively low knowledge of normal intracranial EEG activity, a lack of standardized electrode placement—which means a personalized positioning has to be planned for each patient based on the suspected localizing area within the brain—the necessity of sophisticated analysis techniques (beyond the methods used for scalp EEG), and knowledge of more complex, region-specific activity patterns in the brain (Frauscher et al., 2018).

• Ethical concerns in invasive research and experimentation: SEEG research at the current time is ethically acceptable only in patients with a clinical need for invasive EEG techniques, ensuring the clinical decision isn't research-driven. Due to risks, research protocols that alter electrode placement for scientific aims require high ethical scrutiny (Chiong et al., 2018).

6. Advantages of SEEG over other intracranial monitoring methods

Minimally invasive nature compared to subdural EEG

There are two methods for intracranial EEG: subdural EEG (SDE) and stereotactic EEG (using depth electrodes). Subdural EEG requires the removal of a portion of the skull (craniotomy) to insert electrode grids over the surface of the cortex to measure (and/or modulate) the brain's electrical field.

Compare this to SEEG, where tiny holes (a few mm) are made to insert the electrodes. Thus, minimal surgical exposure leads to less pain and better post-operative recovery (Katz & Abel, 2019).

Better safety profile

SDE involves an open craniotomy for grid placement, which inherently carries a higher risk of injury to tissues with larger extra-axial fluid collections, whereas SEEG is performed via small burr holes, limiting tissue disruption. Based on clinical data available, SEEG is generally considered the safer invasive monitoring technique in modern practice, with similarly very low mortality but significantly lower morbidity than SDE (markedly lower rates of hemorrhage, infection, and neurological deficits) (Arya et al., 2013; Mullin et al., 2016).

The table below summarizes the safety profile:

	SEEG	SDE
Hemorrhage	Prevalence of 1.0% (95% CI 0.6–1.4%)	Prevalence of 4.0% (95% CI 3.2–4.8)
Infection	Prevalence is 0.8% (95% CI is 0.3–1.2%) Cerebral abscess was most common, with a prevalence of 0.9% (95% CI 0.2–1.6%)	Neurologic infections were seen in 2.3% (95% CI: 1.5–3.1) of cases. Superficial wound infections in ~3.0% (95% CI: 1.9–4.1)
Mortality	0.19% mortality (5 deaths among 2624 patients)	0.19% mortality (approximately 5 deaths among 2542 patients)​

The morbidity profile of SEEG was typically highly favorable, exhibiting significantly fewer overall complications compared to SDE.

Better localization of deep-seated epileptic foci

Stereo-EEG, while having relatively sparse sampling on the cortical surface, offers the ability to access the depth of sulci, mesial and basal surfaces of cerebral hemispheres, and deep structures such as the insula, which are largely inaccessible to subdural electrodes (Katz & Abel, 2019). 

7. Future Directions in SEEG

Advancements in electrode technology

Recent research is focused on developing smaller, more flexible, durable, and biocompatible materials to minimize brain injury and scarring and allow more accurate and longer study durations (Zhang et al., 2025).

ML/AI in SEEG data analysis

AI/ML-driven software is already helping clinicians in various steps of SEEG placement. Augmented reality (AR) or virtual reality (VR) may soon be incorporated as technology advances. Furthermore, EEG software will better detect anomalous brain waves, including epileptiform waves, and help cut down labor associated with interpreting vast amounts of output data (Dasgupta et al., 2022).

8. Conclusion

Over the years, SEEG has gradually become an advanced, electrophysiological tool to record electrical activity from deep brain structures with unmatched precision. It has created a new way for clinicians to approach the diagnosis and management of drug-resistant epilepsy.

SEEG offers superior spatial resolution, greater safety, and enhanced patient comfort compared to other intracranial monitoring methods, like subdural EEG. Beyond diagnosis and pre-surgical planning, SEEG is now increasingly recognized for its potential in research, like Brain–Computer Interfaces and Deep Brain Stimulation. As electrode technology and AI/ML software mature, the applications of SEEG are expected to expand even further. It may give us a more in-depth understanding of our brain's neural circuits to help us better understand the electrical brain function.

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