Acute Recording of Stereotyped High-Frequency Oscillations

Acute Recording of Stereotyped High-Frequency Oscillations With a Closed-Loop Brain Interchange System in Drug-Resistant Epilepsy

Overall, this study will investigate the functional utility of stereotyped HFOs by capturing them with a new implantable system (Brain Interchange - BIC of CorTec), which can sample neural data at higher rates >=1kHz and deliver targeted electrical stimulation to achieve seizure control. In contrast to current closed-loop systems (RNS), which wait for the seizure to start before delivering stimulation, the BIC system will monitor the spatial topography and rate of stereotyped HFOs and deliver targeted stimulation to these HFO generating areas to prevent seizures from occurring. If the outcomes of our research in an acute setting become successful, the investigators will execute a clinical trial and run the developed methods with the implantable BIC system in a chronic ambulatory setting.

Study Overview

• Status: Active, not recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Device: Brain Interchange System

Detailed Description

High-frequency oscillations (HFOs) of intracranial EEG (iEEG) have the potential to identify the surgical resection area/seizure onset zone (SOZ) in patients with drug-resistant epilepsy. However, multiple reports indicate that HFOs can be generated not only by epileptic cerebral tissue but also by non-epileptic sites often including eloquent regions such as motor, visual, and language cortices. In this project, the initial evidence of a recurrent waveform pattern is presented that may be sufficient to distinguish pathological HFOs from physiological ones. Specifically, the investigators show that the SOZ repeatedly generates sets of stereotypical HFOs with similar waveform morphology whereas the events recorded from out of SOZ were irregular. This morphological pattern served as a robust neurobiomarker to isolate SOZ from other brain areas in multiple patients consistently. While these promising preliminary results are in place, the functional utility of stereotyped HFOs in a closed-loop seizure control system remains unknown. As of today, not much is known whether the stereotyped HFOs generated by the SOZ can be detected with an implantable system. If this can be achieved, then HFOs can be strategically translated as a neurobiomarker into closed-loop seizure control applications. The investigators hypothesize that pathologic stereotyped HFOs can be captured with the implantable Brain Interchange (BIC) system of CorTec and spatial topography of these events can be utilized by the implantable system to deliver targeted electrical stimulation to achieve seizure control. Using an acute setup within the epilepsy monitoring unit (EMU), this project will investigate the feasibility of capturing stereotyped HFO events using the new BIC system and compare the detection results to those obtained with the commercially available amplifier (Aim-1). If the first phase (Aim-1) of the study becomes successful, later in the second phase (Aim-2), once again in the EMU, the investigators will deliver targeted electrical stimulation to those brain sites associated with stereotyped HFOs using the BIC.

During the entire study, the BIC system will not be implanted but used externally to assess the neural data through externalized electrodes and then deliver closed-loop stimulation. If the outcomes of the research in an acute setting become successful, the investigators will execute a clinical trial and run our methods with the implanted BIC system in a chronic ambulatory setting.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Texas
    • Houston, Texas, United States, 77030-3498
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients with medically refractory epilepsy, who have been deemed appropriate candidates for intracranial EEG monitoring
• Adult men and women (18≤ age <70 years)
• children (3≤ age <18 years)
• includes women and minorities

Exclusion Criteria:

• Subjects will be excluded if their condition makes them unable to continue with recordings.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Epilepsy; patients with drug resistant epilepsy undergoing a surgical evaluation in the epilepsy monitoring unit

Device: Brain Interchange System; The CorTec Brain Interchange (BIC) is an implantable system with sensing and stimulation capability dedicated to promoting brain computer interface and closed-loop neuromodulation research. It is an externally powered implant which can provide neural data to a nearby computing station (communication unit connected to a personal computer) continuously. In return, computing station controls the implant e.g. for generating therapeutic electrical stimulation to the brain. It is expected that BIC will catalyze translational applications of electroceuticals in human subject by making the neural data immediately available as well as permit the investigation of novel closed-loop neuromodulation applications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Robustness in Data Transmission	Outcome-1 will quantify the feasibility of robust data recording and transmission with the BIC system in the epilepsy monitoring unit (EMU). The investigators will develop software tools to communicate with the BIC directly from MATLAB and Simulink. The incoming data from the implantable system will be visualized with gHIsys, the high-speed data processing libraries of gTec. At the end of the first year, in the epilepsy monitoring unit (EMU), the investigators will test the feasibility of recoding iEEG data from 2 patients continuously over 24 hours with less than <5% data loss. The BIC system will not be implanted but used externally to record the neural data. The research team will also test to record iEEG/ECoG data simultaneously with 2 BIC units to be ready for those cases where the number of recording channels are larger than =>32 and <=64. At this stage Outcome-1 is only related to the device feasibility (robust data transmission) not health related outcome.	Over 24 hours within the first year of project
Feasibility of Detection of Stereotyped HFOs	Outcome-2 will test the feasibility of capturing stereotyped HFO (sHFO) with the BIC system in the EMU setting. Once the feasibility of robust data transmission as listed in (Outcome-1) is tested, the neural activity will be recorded over 24 hours using the BIC system from 10 patients. The hardware will not be implanted but used externally to record the neural data. Then, the research team will compare whether the sHFO detection and SOZ localization accuracy is significantly different between the BIC and FDA approved amplifier. If the investigators can detect stereotyped HFOs with a rate not less than 75% of FDA approved clinical amplifier and predict the SOZ in 8/10 patients, then the research team will move to the second phase of the project to test Outcome-3. Outcome-2 tests the feasibility of capturing relevant neural events with the external BIC system and compares the recording quality to the FDA approved amplifiers. Outcome-2 does not test any health-related outcome.	Within the first 3 years of the project

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Baylor College of Medicine; National Institute of Neurological Disorders and Stroke (NINDS); CorTec GmbH

Publications and helpful links

General Publications

• Ayyoubi AH, Fazli Besheli B, Quach MM, Gavvala JR, Goldman AM, Swamy CP, Bartoli E, Curry DJ, Sheth SA, Francis DJ, Ince NF. Benchmarking signal quality and spatiotemporal distribution of interictal spikes in prolonged human iEEG recordings using CorTec wireless brain interchange. Sci Rep. 2024 Feb 8;14(1):2652. doi: 10.1038/s41598-024-52487-5.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: June 19, 2022
• First Submitted That Met QC Criteria: June 26, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Epilepsy; Neuromodulation; Machine Learning; HFO; Closed-Loop
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: 23-008859; 1UH3NS117944-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Intracranial EEG + ECoG recorded from patients with epilepsy will be shared. The electrical signs of neural activity will be collected in the EMU for 24hrs. One stream of data will be digitized at 1kHz with 16bit resolution with the BIC system and the other stream with least a 2 kHz sampling frequency to capture HFOs reaching up to 500Hz.

All collected data will be de-identified prior to data exchange. Patient data will be provided in a coded format that protects patient identities but will contain diagnosis (signs/symptoms), interventions including technical observations, diagnostic tests/results, and patient outcomes.

Information about the recording device including device serial numbers, device model numbers, date of the event, and country/state of the event will be annotated with the data.

• IPD Sharing Time Frame: Every 6 months
• IPD Sharing Access Criteria: Data Archive for the BRAIN Initiative (DABI) - invasive human neurophysiology (including EEG, ECoG, LFP, single unit)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No