US-12616840-B2 - Systems and methods for seizure detection and closed-loop neurostimulation

US12616840B2US 12616840 B2US12616840 B2US 12616840B2US-12616840-B2

Abstract

Embodiments described herein relate to systems, devices, and methods for monitoring brain activity and delivering electrical brain stimulation to a patient. In some embodiments, a system can deliver responsive electrical stimulation in a closed-loop manner and can offer real-time or near real-time monitoring of induced neurophysiological effects. After detecting a targeted brain pattern (i.e., an epileptic seizure), the system may deliver high-intensity ultra-short electrical stimulation impulses non-invasively or minimal-invasively to diminish or stop the neural oscillations underlying the epileptic seizure. The stimuli are delivered in time and space, relative to the emerging seizure rhythm patterns, such that they diminish or terminate the seizure. The system may include an implantable device including one or more electrodes electrically coupled to one or more processors. The processor(s) may be operatively coupled to a memory, one or more communication modules, and may optionally be coupled to a battery and one or more additional sensor(s).

Inventors

Antal BERÉNYI
Tamás KURICS
Miklós BENCE
Máté NÉMETH
Tamás LASZLOVSZKY
Mihály NÁDASDI
Péter RÁFI
Viktor VINCZE
Szabolcs Hőgye

Assignees

BLACKROCK MICROSYSTEMS, INC.

Dates

Publication Date: 20260505
Application Date: 20241213

Claims (20)

1 . A system, comprising: a plurality of electrodes configured for implantation in a patient and configured to measure a brain activity of the patient; a memory; and one or more processors operatively coupled to the memory and the plurality of electrodes, the one or more processors configured to: receive brain activity data from the plurality of electrodes; detect an onset of a seizure based on the brain activity data; identify a pattern in the brain activity data based on mutual information between one or more pairs of electrodes from the plurality of electrodes, the mutual information determined, at least in part, by: computing covariances between signals from the one or more pairs of electrodes from the plurality of electrodes, generating a first value based on the covariances, normalizing the first value to generate a second value r sq , and calculating a logarithm of (1−r sq ); determine, based on the pattern in the brain activity data, a timing with which to deliver current pulses to a brain of the patient to disrupt at least one oscillation in brain activity contributing to the seizure; and activate a subset of electrodes from the plurality of electrodes to deliver the current pulses to a target region of the brain of the patient according to the timing.
2 . The system of claim 1 , wherein the brain activity data includes electroencephalography (EEG) data.
3 . The system of claim 1 , wherein a subset of electrodes from the plurality of electrodes is implanted in one of a subgaleal space of the patient, a subdural space of the patient, an epidural space of the patient, or the brain of the patient.
4 . The system of claim 1 , wherein the plurality of electrodes is configured to deliver Intersectional Short-Pulse (ISP) stimulation to disrupt the at least one oscillation in brain activity contributing to the seizure.
5 . The system of claim 1 , wherein the one or more processors is configured to determine the timing based on at least one of a phase or a frequency of the brain activity data, and to activate the subset of electrodes to deliver the current pulses one of immediately or after a predetermined delay, and with a predefined frequency.
6 . The system of claim 1 , wherein the one or more processors is further configured to activate the subset of electrodes to deliver the current pulses one of immediately or after a predetermined delay, the one or more current pulses configured to align with an inherent rhythmicity of the brain activity data.
7 . The system of claim 1 , further comprising: a sensor configured to measure biosignal data associated with the patient, the one or more processors configured to detect a precursor activity leading to a seizure, the onset of the seizure, or a presence of the seizure further based on the biosignal data.
8 . The system of claim 7 , wherein the sensor is configured to measure at least one of electromyography (EMG) data, electrocardiogram (ECG) data, or heart rate.
9 . The system of claim 1 , wherein the one or more processors is further configured to quantify the pattern in the brain activity data by calculating a measure of rhythmicity at predetermined frequency components of the brain activity data.
10 . The system of claim 1 , further comprising: a communication interface configured to transfer information between the one or more processors and an external device, the external device configured to train a model for detecting a precursor activity leading to a seizure, the onset of the seizure, or a presence of the seizure, the model configured to be executed by the one or more processors.
11 . The system of claim 10 , wherein the model is trained using datasets including ictal EEG data and non-ictal EEG data from at least one of the patient or another patient.
12 . An implantable neurostimulator device, comprising: a memory; and a processor operatively coupled to the memory, the processor configured to be electrically coupled to a plurality of electrodes implanted in a patient, the processor configured to: receive brain activity data from the plurality of electrodes; detect a precursor activity leading to a seizure, an onset of the seizure, or a presence of the seizure based on the brain activity data; identify a pattern in the brain activity data based on mutual information between one or more pairs of electrodes from the plurality of electrodes, the mutual information determined, at least in part, by: computing covariances between signals from the one or more pairs of electrodes from the plurality of electrodes, generating a first value based on the covariances, normalizing the first value to generate a second value r sq , and calculating a logarithm of (1−r sq ); determine a timing with which to deliver current pulses to a brain of the patient to interfere with at least one oscillation in brain activity contributing to the seizure based on the pattern in the brain activity data; and activate a subset of electrodes from the plurality of electrodes to deliver the current pulses to a target region of the brain of the patient based on the timing.
13 . The implantable neurostimulator device of claim 12 , wherein the brain activity data includes electroencephalography (EEG) data.
14 . The implantable neurostimulator device of claim 12 , wherein at least a subset of electrodes from the plurality of electrodes is implanted in one of a subgaleal space of the patient, a subdural space of the patient, an epidural space of the patient, or the brain of the patient.
15 . The implantable neurostimulator device of claim 12 , wherein the plurality of electrodes is configured to deliver Intersectional Short-Pulse (ISP) stimulation, and each of the current pulses has an amplitude of about 0.1 milliamps (mA) to about 80 mA.
16 . The implantable neurostimulator device of claim 12 , wherein the processor is configured to determine the timing based on one of a measure of rhythmicity in the brain activity data or a feature of the rhythmicity in the brain activity data, and to activate the subset of electrodes to deliver the current pulses one of immediately or after a predetermined delay, and with a predefined frequency.
17 . The implantable neurostimulator device of claim 12 , wherein the processor is further configured to activate the subset of electrodes to deliver the current pulses one of immediately or after a predetermined delay, the current pulses configured to align with an inherent rhythmicity of the brain activity data.
18 . The implantable neurostimulator device of claim 12 , further comprising: one or more sensors configured to measure biosignal data associated with the patient, the processor configured to detect the precursor activity leading to the seizure, the onset of the seizure, or the presence of the seizure further based on the biosignal data.
19 . A method, comprising: measuring brain activity data associated with a brain of a patient using a plurality of electrodes implanted in the patient; detecting a precursor activity leading to a seizure, an onset of the seizure, or a presence of the seizure based on the brain activity data; identifying a pattern in the brain activity data based on mutual information associated with the plurality of electrodes, the mutual information determined, at least in part, by: computing covariances between signals associated with the plurality of electrodes, generating a first value based on the covariances, normalizing the first value to generate a second value r sq , and calculating a logarithm of (1−r sq ); determining, based on the pattern in the brain activity data, a timing with which to deliver electrical stimulation to the brain of the patient to disrupt oscillations in brain activity contributing to the seizure; and in response to detecting the precursor activity leading to a seizure, the onset of the seizure, or the presence of the seizure, causing delivery of electrical stimulation to the brain of the patient via at least a subset of electrodes from the plurality of electrodes and according to the timing.
20 . The method of claim 19 , wherein the brain activity data includes electroencephalography (EEG) data collected from a plurality of EEG channels.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Application 63/610,955, titled “SYSTEMS AND METHODS FOR SEIZURE DETECTION AND CLOSED-LOOP NEUROSTIMULATION” and filed Dec. 15, 2023, the disclosure of which is incorporated by reference herein in its entirety. TECHNICAL FIELD Embodiments described herein relate to systems, devices, and methods for monitoring brain activity and delivering electrical brain stimulation to a patient. More specifically, one or more embodiments described herein relate to monitoring brain activity to detect an onset of a seizure and to deliver electrical stimulation to inhibit the seizure. BACKGROUND High intensity neurostimulation can alter brain activity in a nearly instantaneous manner and can be used to terminate epileptic seizures. It is preferable to terminate initiation of seizures as soon as possible before the seizures generalize and before behavioral symptoms develop. In order to terminate a seizure, a system should be capable of fast/early recognition of seizure patterns (short detection delay), highly reliable seizure recognition (high sensitivity), and a low false alarm rate (high specificity). Achieving a low false alarm rate is important to avoid unnecessary stimulation of the brain, as high intensity stimulation may deplete battery and may cause inconvenience to patients. Known real-time seizure detector algorithms lack these capabilities, and as such, novel approaches and improved detection methodologies are needed to improve detector performance and facilitate closed-loop neurostimulation in epilepsy and other brain disorders. SUMMARY In some embodiments, a system comprises a plurality of electrodes configured for implantation in a patient and configured to measure a brain activity of the patient; a memory; and one or more processors operatively coupled to the memory and the plurality of electrodes. The one or more processors configured to receive brain activity data from the plurality of electrodes; detect an onset of a seizure based on the brain activity data; determine, based on a pattern in the brain activity data, a timing with which to deliver current pulses to a brain of the patient to disrupt at least one oscillation in brain activity contributing to the seizure; and activate a subset of electrodes from the plurality of electrodes to deliver the current pulses to a target region of the brain of the patient according to the timing. In some embodiments, the brain activity data includes electroencephalography (EEG) data. In some embodiments, the plurality of electrodes includes between 1 electrode contacts and 256 electrode contacts. In some embodiments, at least a subset of electrodes from the plurality of electrodes is implanted in one of a subgaleal space of the patient, a subdural space of the patient, an epidural space of the patient, or the brain of the patient. In some embodiments, the plurality of electrodes is implanted in a subgaleal space of the patient. In some embodiments, the plurality of electrodes is configured to deliver Intersectional Short-Pulse (ISP) stimulation. In some embodiments, each of the current pulses has an amplitude of about 0.1 mA to about 80 mA. In some embodiments, the one or more processors is configured to determine the timing based on at least one of a phase or a frequency of the brain activity data, and to activate the subset of electrodes to deliver the current pulses one of immediately or after a predetermined delay, and with a predefined frequency. In some embodiments, the one or more processors is further configured to recognize the pattern of brain activity, the one or more processors is configured to activate the subset of electrodes to deliver the current pulses one of immediately or after a predetermined delay, the one or more current pulses configured to align with an inherent rhythmicity of the brain activity data. In some embodiments, the one or more processors includes at least one of a field-programmable gate array (FPGA) chip or a microcontroller. In some embodiments, the system further comprises a battery configured to supply power to each of the processor, the memory, and the plurality of electrodes. In some embodiments, the battery is implanted in a chest of the patient. In other embodiments, the battery is disposed on a head of the patient. In some embodiments, the system further comprises one or more sensors configured to measure biosignal data associated with the patient, the one or more processors configured to detect a precursor activity leading to a seizure, the onset of the seizure, or a presence of the seizure further based on the biosignal data. In some embodiments, the one or more sensors are configured to measure at least one of electromyography (EMG) data, electrocardiogram (ECG) data, or heart rate. In some embodiments, the one or more processors is further configured to quantify the pattern in the brain activity data by calculatin