Methods, systems, and apparatus for closed-loop neural control

Abstract

Systems, devices, and methods for treating drug-refractory epilepsy are disclosed. [Solution] In one embodiment, a method for treating epilepsy is disclosed, comprising detecting electrophysiological signals of a subject using a first electrode array coupled to a first intravascular carrier. The method further comprises analyzing the electrophysiological signals using a neuromodulator electrically coupled to the first electrode array, and stimulating a target site in the subject's body using a second electrode array coupled to a second intravascular carrier implanted in a portion of a body blood vessel above the base of the subject's skull.

Description

Technical Field

[0001] The present disclosure generally relates to intravascular neuromodulation. More specifically, the present disclosure relates to methods, systems, and devices for closed-loop intravascular neuromodulation.

Background Art

[0002] Vagus nerve stimulation has been successful in reducing seizure frequency in medically refractory epilepsy patients and patients for whom resection options are not suitable. Vagus nerve stimulation devices (VNS) have been implanted in more than 100,000 humans, but their treatment results are moderate. The responder rate, which is the proportion of patients with a seizure frequency reduction greater than 50%, is only 46.6%, and the median seizure reduction is 52.4%. In addition, since a cuff-shaped electrode is directly implanted around the vagus nerve, there may be side effects such as nerve damage and paralysis, and direct damage to the neck that requires a surgical incision to expose the nerve for electrode implantation.

[0003] Current VNS stimulation parameters are often open-loop, which means that stimulation is performed according to a continuous or strict schedule. Generally, stimulation is applied for about 1 to 5 minutes and then rested for about 4 to 10 minutes. Therefore, there are concerns about battery consumption and hardware failure in order to supply a large amount of power. In either case, an additional operation to remove any implanted unit is required for battery replacement or replacement of a failed hardware component. Also, recent research has focused on some potential side effects associated with such continuous or constant stimulation. See, for example, Non-Patent Documents 1 and 2.

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

[0005] Therefore, solutions are needed to address the aforementioned shortcomings and disadvantages of conventional neural control systems. Such solutions must be safe, effective, and not excessively difficult to transplant. [Means for solving the problem]

[0006] Systems, apparatus, and methods for treating drug-refractory epilepsy are disclosed. In one embodiment, a method for treating epilepsy includes detecting electrophysiological signals from a subject using a first electrode array. The first electrode array can be coupled to a first intravascular carrier implanted in the subject's body. The method may also include analyzing electrophysiological signals using a neuromodulator implanted in the subject's body and electrically coupled to the first electrode array, and stimulating a target site in the subject's body using a second electrode array in response to the detected electrophysiological signals. The second electrode array may be electrically coupled to the neuromodulator. The second electrode array may be coupled to a second intravascular carrier implanted in a portion of a body blood vessel above the base of the subject's skull.

[0007] Stimulating a target site within the body may further include generating electrical impulses using a pulse generator electrically coupled to a second electrode array. The pulse generator can be implanted in the subject's body. Generating electrical impulses may further include increasing the current amplitude of the electrical impulse from 0 mA to a maximum of 10 mA in increments of 0.1 mA, and increasing the voltage of the electrical impulse from 0 V to a maximum of 10 V in increments of 0.25 V. Furthermore, the pulse width of the electrical impulse may be set from 25 μS to approximately 600 μS. In addition, the frequency of the electrical impulse may be set from 1 Hz to 400 Hz.

[0008] In some embodiments, the method may also include delivering a first intravascular carrier and a second intravascular carrier through a single delivery catheter prior to detecting the subject's electrophysiological signals. In another embodiment, the method may include delivering a first intravascular carrier through a first delivery catheter and delivering a second intravascular carrier through a second delivery catheter prior to detecting the subject's electrophysiological signals. In a further embodiment, the method may include delivering a first intravascular carrier through a first delivery catheter and delivering a second intravascular carrier through a second delivery catheter extending through the first delivery catheter.

[0009] In some embodiments, the method may further include stimulating a target site in the subject's body using a first electrode array. In these embodiments, the method may further include using a second electrode array to detect or record the subject's electrophysiological signals.

[0010] Also disclosed are intravascular neuromodulatory systems for treating epilepsy and / or other conditions or disorders. The system may comprise a first electrode array configured to detect electrophysiological signals from a subject. The first electrode array may be coupled to a first intravascular carrier configured to be implanted in the subject's body. The system may further comprise a second electrode array configured to stimulate a target site in the subject's body. The second electrode array may be coupled to a second intravascular carrier configured to be implanted above the base of the subject's skull. The system may further comprise an implantable neuromodulator electrically coupled to the first and second electrode arrays.

[0011] The neural control unit may be configured to analyze the electrophysiological signals detected by the first electrode array and generate electrical impulses via a pulse generator to be transmitted to the second electrode array to stimulate a target site in the body in response to the detected electrophysiological signals.

[0012] A first intravascular carrier carrying a first electrode array may be implanted in or configured to be implanted in a subject's venous sinus. For example, the first intravascular carrier may be implanted in or configured to be implanted in at least one of the subject's superior sagittal sinus, inferior sagittal sinus, sigmoid sinus, transverse sinus, and straight sinus.

[0013] In some embodiments, the first intravascular carrier may be implanted in or configured to be implanted in a superficial cerebral vein. For example, the first intravascular carrier may be implanted in or configured to be implanted in at least one of the following veins: Rabe's vein, Trollado's vein, Sylvian's vein, and Rolandic's vein.

[0014] In other embodiments, the first endovascular carrier may be implanted in or configured to be implanted in a deep cerebral vein. For example, the first endovascular carrier may be implanted in or configured to be implanted in at least one of the Rosenthal vein, Galen vein, superior thalamostriate vein, and internal cerebral vein.

[0015] Furthermore, the first intravascular carrier may be implanted in at least one of the central sulcal vein, post-central sulcal vein, and pre-central sulcal vein. In some embodiments, the first intravascular carrier may be implanted or configured to be implanted in a vessel extending through the subject's hippocampus or amygdala.

[0016] The target site within the body may be a portion of the subject's vagus nerve. The second endovascular carrier may be implanted in, or configured to be implanted in, a portion of the internal jugular vein superior to the subject's jugular foramen. The second endovascular carrier may be implanted in, or configured to be implanted in, a branch or tributary of the internal jugular vein. The second endovascular carrier may also be implanted in a portion of the internal carotid artery superior to the subject's skull base.

[0017] In some embodiments, the target site within the body may be the subject's cerebellum. In these embodiments and other embodiments, the second intravascular carrier may be implanted or configured to be implanted in at least one of the subject's sigmoid sinuses, transverse sinuses, and straight sinuses.

[0018] In other embodiments, the target site within the body may be the motor cortex of the subject. In these and other embodiments, the second intravascular carrier may be implanted in or configured to be implanted in at least one of the superior sagittal sinus, inferior sagittal sinus, central sulcus vein, posterior central sulcus vein, and anterior central sulcus vein.

[0019] The second endovascular carrier may be implanted in or configured to be implanted in a superficial cerebral vein. For example, the second endovascular carrier may be implanted in or configured to be implanted in at least one of the following veins: Rabet's vein, Trollard's vein, Sylvian vein, and Rolandic vein.

[0020] Furthermore, the second endovascular carrier may be implanted in or configured to be implanted in a deep cerebral vein. For example, the second endovascular carrier may be implanted in or configured to be implanted in at least one of the Rosenthal vein, Galen vein, superior thalamostratum vein, and internal cerebral vein. In these and other embodiments, the target site in the body may be at least one of the anterior thalamus, central thalamic nucleus, fornix, hippocampus, hypothalamus, subthalamic nucleus, and posterior caudal zone incerta. In some embodiments, the second endovascular carrier may be implanted in or configured to be implanted in a vessel extending through the subject's hippocampus or amygdala.

[0021] Regarding the implantation site, the first endovascular carrier carrying the first electrode array and the second endovascular carrier carrying the second electrode array can be implanted in any combination of the internal blood vessels disclosed herein. For example, the first endovascular carrier may be implanted in a venous sinus and the second endovascular carrier in a superficial cerebral vein. Alternatively, for example, the first endovascular carrier may be implanted in a deep cerebral vein and the second endovascular carrier in an internal jugular vein.

[0022] Furthermore, the neural modulator may be implanted in or configured to be implanted within the subject's body. For example, the neural modulator may be implanted in or configured to be implanted within the subject's forearm. Alternatively, the neural modulator may be implanted in or configured to be implanted within the subject's chest. Alternatively, the neural modulator may be implanted in or configured to be implanted within the subject's armpit.

[0023] The first electrode array can be electrically coupled to the neuromodulation unit via a first transmission lead having a first lead diameter. The first transmission lead can penetrate the neck muscles of the subject. The diameter of the first lead can be about 0.5 mm to 1.5 mm. The second electrode array can be electrically coupled to the neuromodulation unit via a second transmission lead having a second lead diameter. The second transmission lead can extend through the neck of the subject. The second lead diameter can be about 0.5 mm to 1.5 mm. In other embodiments, the first electrode array and the second electrode array can be coupled to the neuromodulation unit via a single transmission lead having a lead diameter. The single transmission lead can extend through the neck of the subject. In these embodiments, the lead diameter can be about 0.5 mm to 1.5 mm.

[0024] In some embodiments, the pulse generator can be part of the neuromodulation unit. The pulse generator can be powered and operated by an external device. For example, the pulse generator can include a first magnetic component, and the external device can include a second magnetic component configured to be magnetically coupled to the first magnetic component. The pulse generator can be configured to be charged from the external device by electromagnetic induction when the external device is placed in the vicinity of the pulse generator.

[0025] In these and other embodiments, the neuromodulation unit can be powered by one or more batteries. The external device can be provided as part of an armband when implanting the neuromodulation unit into the subject's arm.

[0026] At least one of the first intravascular carrier and the second intravascular carrier can be an expandable stent or an intravascular scaffold including an electrode array coupled to the expandable stent or the intravascular scaffold. For example, at least one of the first intravascular carrier and the second intravascular carrier can be a self-expanding stent or a self-expanding intravascular scaffold.

[0027] At least one of the first and second intravascular carriers may be a wire or cable configured to be wound or coiled, including an electrode array, the electrode array being coupled to the wire or cable. The wire or cable can be wound substantially helically. In some embodiments, at least one of the first and second intravascular carriers may be a wire or cable including a sharp distal end for penetrating the lumen or vessel wall. Furthermore, at least one of the first and second intravascular carriers may be a wire or cable constituting an anchor. For example, the anchor may be at least one of a barbed anchor and a radially expandable anchor.

[0028] The neural control unit may further comprise a telemetry unit. The telemetry unit may be configured to analyze detected electrophysiological signals by comparing them to one or more signal thresholds or patterns. In some embodiments, the electrophysiological signals may be local potentials (LFPs) and / or intracranial / cortical EEGs measured in the subject's brain. In these embodiments and other embodiments, the electrophysiological signals may be cortical electroencephalogram signals.

[0029] The first intravascular carrier, the second intravascular carrier, and / or the transmission lead can be formed in part from platinum-tungsten, gold, aluminum, nitinol wire, rhodium, iridium, nickel, nickel-chromium alloy, gold-palladium-rhodium alloy, chromium-nickel-molybdenum alloy, and / or stainless steel.

[0030] Another method for treating epilepsy is also disclosed. This method may include detecting electrophysiological signals from a subject using a first electrode array. The first electrode array may be bound to an intravascular carrier implanted above the base of the subject's skull. This method may further include analyzing the electrophysiological signals using a neural modulator electrically coupled to the first electrode array. This method may further include stimulating a target site in the subject's body using a second electrode array in response to the detected electrophysiological signals. The second electrode array may be bound to the same intravascular carrier.

[0031] Furthermore, the electrodes of the second electrode array are separate from the electrodes of the first electrode array. In some embodiments, the first and second electrode arrays can record or transmit data to the neural control unit via different channels.

[0032] Stimulating a target site in the body may further include generating an electrical impulse using a pulse generator electrically coupled to a second electrode array. The pulse generator may be implanted in the subject's body. Stimulating a target site in the body may further include generating an electrical impulse using a pulse generator electrically coupled to a second electrode array. Generating an electrical impulse may further include increasing the current amplitude of the electrical impulse from 0 mA to a maximum of 10 mA in increments of 0.1 mA, and increasing the voltage of the electrical impulse from 0 V to a maximum of 10 V in increments of 0.25 V. Furthermore, the pulse width of the electrical impulse may be set from 25 μS to approximately 600 μS. Furthermore, the frequency of the electrical impulse may be set from 1 Hz to 400 Hz.

[0033] Also disclosed are other intravascular neuromodulatory systems for treating epilepsy and / or other conditions or disorders. The system may comprise a first electrode array configured to detect electrophysiological signals from a subject. The first electrode array may be coupled to an intravascular carrier configured to be placed intravascularly above the base of the subject's skull. The system may further comprise a second electrode array configured to stimulate a target site within the subject's body. The second electrode array may be coupled to the same intravascular carrier. The system may further comprise an implantable neuromodulator electrically coupled to the first and second electrode arrays.

[0034] The neural control unit may be configured to analyze the electrophysiological signals detected by the first electrode array and generate electrical impulses via a pulse generator to be transmitted to the second electrode array to stimulate a target site in the body in response to the detected electrophysiological signals.

[0035] The target site within the body may be a portion of the subject's vagus nerve. The endovascular carrier may be implanted, or configured to be implanted, within a portion of the internal jugular vein superior to the subject's jugular foramen. In some embodiments, the endovascular carrier may be implanted, or configured to be implanted, within a branch or tributary of the internal jugular vein. The endovascular carrier may also be implanted, or configured to be implanted, within a portion of the internal carotid artery superior to the subject's skull base.

[0036] In some embodiments, the target site within the body may be the subject's cerebellum. In these embodiments, the intravascular carrier may be implanted or configured to be implanted in at least one of the subject's sigmoid sinuses, transverse sinuses, and straight sinuses.

[0037] In other embodiments, the target site within the body may be the motor cortex of the subject. In these embodiments, the intravascular carrier may be implanted in or configured to be implanted in at least one of the superior sagittal sinus, inferior sagittal sinus, central sulcus vein, posterior central sulcus vein, and anterior central sulcus vein.

[0038] Furthermore, the endovascular carrier can be implanted in the superficial cerebral veins. For example, the endovascular carrier can be implanted in or configured to be implanted in at least one of the following veins: the Rabe vein, the Trollado vein, the Sylvian vein, and the Rolandic vein.

[0039] The endovascular carrier may be implanted or configured to be implanted within the deep cerebral veins. For example, the endovascular carrier may be implanted or configured to be implanted within at least one of the Rosenthal vein, Galen vein, superior thalamostriate vein, and internal cerebral vein.

[0040] Furthermore, the neural modulator may be implanted in or configured to be implanted within the subject's body. For example, the neural modulator may be implanted in or configured to be implanted within the subject's forearm. Alternatively, the neural modulator may be implanted in or configured to be implanted within the subject's chest. Alternatively, the neural modulator may be implanted in or configured to be implanted within the subject's armpit.

[0041] A first electrode array may be electrically coupled to a neuromodulator via a first transmission lead having a first lead diameter. The first transmission lead may extend through the neck of the subject. The first lead diameter may be approximately 0.5 mm to 1.5 mm. A second electrode array may be electrically coupled to a neuromodulator via a second transmission lead having a second lead diameter. The second transmission lead may extend through the neck of the subject. The second lead diameter may be approximately 0.5 mm to 1.5 mm.

[0042] In other embodiments, the first and second electrode arrays may be coupled to a neuromodulator via a single transmission lead having a lead diameter. The single transmission lead may extend through the neck of the subject. In these embodiments, the lead diameter may be approximately 0.5 mm to 1.5 mm.

[0043] In some embodiments, the pulse generator may be part of the neural modulator. The pulse generator may be powered and operated by an external device. For example, the pulse generator may include a first magnetic component, and the external device may include a second magnetic component configured to be magnetically coupled to the first magnetic component. The pulse generator may be configured to be charged by electromagnetic induction from the external device when the external device is placed in the vicinity of the pulse generator.

[0044] In these and other embodiments, the neural modulator may be powered by one or more batteries. The external device may be provided as part of an armband when the neural modulator is implanted in the subject's arm.

[0045] In some embodiments, the intravascular carrier may be an expandable stent or intravascular scaffold including an electrode array, the electrode array being coupled to the expandable stent or intravascular scaffold. For example, the intravascular carrier may be a self-expanding stent or self-expanding intravascular scaffold.

[0046] In other embodiments, the intravascular carrier may be a wire or cable configured to be wound or coiled, including an electrode array, to which the electrode array is coupled. The wire or cable can be wound substantially spirally.

[0047] In some embodiments, the intravascular carrier may be a wire or cable with a sharp distal end for penetrating the lumen or vessel wall. Furthermore, the intravascular carrier may be a wire or cable constituting an anchor. For example, the anchor may be at least one of a barbed anchor and a radially expandable anchor.

[0048] The neural control unit may further comprise a telemetry unit. The telemetry unit may be configured to analyze detected electrophysiological signals by comparing them to one or more signal thresholds or patterns. In some embodiments, the electrophysiological signals may be local potentials (LFPs) and / or intracranial / cortical EEGs measured in the subject's brain. In these embodiments and other embodiments, the electrophysiological signals may be cortical electroencephalogram signals.

[0049] Intravascular carriers and / or transmission leads may be formed in part from platinum-tungsten, gold, aluminum, nitinol wire, rhodium, iridium, nickel, nickel-chromium alloy, gold-palladium-rhodium alloy, chromium-nickel-molybdenum alloy, and / or stainless steel. [Brief explanation of the drawing]

[0050] [Figure 1] Figure 1 shows an intravascular neuromodulatory system according to one embodiment for treating epilepsy and other diseases / conditions. [Figure 2A] Figures 2A to 2D show intravascular carriers according to various embodiments. [Figure 2B] Figures 2A to 2D show intravascular carriers according to various embodiments. [Figure 2C] Figures 2A to 2D show intravascular carriers according to various embodiments. [Figure 2D] Figures 2A to 2D show intravascular carriers according to various embodiments. [Figure 3A] Figure 3A shows the transplantable sites for the components of the neural regulatory system. [Figure 3B] Figure 3B shows a neural control unit implanted in the subject's arm. [Figure 4A] Figures 4A to 4C show a transmission lead according to one embodiment, used to connect one electrode array to another or to a neural control unit. [Figure 4B]Figures 4A to 4C show a transmission lead according to one embodiment, used to connect one electrode array to another or to a neural control unit. [Figure 4C] Figures 4A to 4C show a transmission lead according to one embodiment, used to connect one electrode array to another or to a neural control unit. [Figure 5A] Figures 5A to 5C show an example of a method for implanting an electrode array according to one embodiment. [Figure 5B] Figures 5A to 5C show an example of a method for implanting an electrode array according to one embodiment. [Figure 5C] Figures 5A to 5C show an example of a method for implanting an electrode array according to one embodiment. [Figure 6] Figure 6 shows a method for treating epilepsy according to one embodiment. [Figure 7] Figure 7 shows a method for treating epilepsy in a different case. [Figure 8A] Figure 8A shows an intravascular carrier according to one embodiment, implanted in the internal jugular vein of a subject. [Figure 8B] Figure 8B is a partial cross-sectional view showing a subject's cross-section at the C6 vertebral level, revealing the vagus nerve and surrounding blood vessels. [Figure 8C] Figure 8C shows the area around the internal jugular vein leading to the vagus nerve. [Figure 9A] Figures 9A to 9G show specific veins and sinuses that can serve as implantation sites for endovascular carriers. [Figure 9B] Figures 9A to 9G show specific veins and sinuses that can serve as implantation sites for endovascular carriers. [Figure 9C] Figures 9A to 9G show specific veins and sinuses that can serve as implantation sites for endovascular carriers. [Figure 9D] Figures 9A to 9G show specific veins and sinuses that can serve as implantation sites for endovascular carriers. [Figure 9E] Figures 9A to 9G show specific veins and sinuses that can serve as implantation sites for endovascular carriers. [Figure 9F] Figures 9A to 9G show specific veins and sinuses that can serve as implantation sites for endovascular carriers. [Figure 9G] Figures 9A to 9G show specific veins and sinuses that can serve as implantation sites for endovascular carriers. [Figure 10] Figure 10 shows a method for deploying or delivering an intravascular carrier according to one embodiment. [Figure 11] Figure 11 shows an example of an intravascular carrier deployment or delivery method. [Figure 12] Figure 12 shows a further example of a method for deploying or delivering an intravascular carrier. [Figure 13] Figure 13 shows a delivery catheter according to one embodiment of a branched transmission lead. [Modes for carrying out the invention]

[0051] The drawings shown and described are illustrative embodiments and are not limiting. Similar reference numerals indicate elements that are identical overall or functionally equivalent.

[0052] Figure 1 shows an intravascular neuromodulatory system 100 according to one embodiment for treating epilepsy and other diseases / conditions. The neuromodulatory system 100 may consist of a plurality of electrode arrays 102 electrically coupled to a neuromodulatory unit 104 via transmission leads 106 or wires. For example, the neuromodulatory system 100 may consist of a first electrode array 102A and a second electrode array 102B electrically coupled to the neuromodulatory unit 104.

[0053] Each of the electrode arrays 102 can be bound to an intravascular carrier 108. For example, a first electrode array 102A can be bound to a first intravascular carrier 108A configured to be implanted intravascularly in the body of a subject. A second electrode array 102B can be bound to a second intravascular carrier 108B configured to be implanted intravascularly in the body of a subject.

[0054] In some embodiments, the first intravascular carrier 108A and the second intravascular carrier 108B may be implanted in different blood vessels (e.g., different veins, arteries, or sinuses) of the subject. In other embodiments, the first intravascular carrier 108A and the second intravascular carrier 108B may be implanted in the same blood vessel or in different locations within the same blood vessel.

[0055] In certain embodiments, the first electrode array 102A may be configured to detect or record electrophysiological signals from a subject, and the second electrode array 102B may be configured to stimulate a target area in the subject's body (e.g., a target nerve, a target brain region or area, or other target tissue). In these embodiments, the neural modulator 104 may be configured to analyze the electrophysiological signals detected or recorded by the first electrode array 102A and to transmit electrical impulses to the second electrode array 102B via the pulse generator 110 in response to the detected or recorded electrophysiological signals.

[0056] In other embodiments, both the first electrode array 102A and the second electrode array 102B may be configured to detect or record the subject's electrophysiological signals. In additional embodiments, both the first electrode array 102A and the second electrode array 102B may be configured to stimulate one or more target sites in the subject's body. One or more target sites in the body will be described in detail in a later section.

[0057] The first electrode array 102A may consist of a plurality of electrodes 112 coupled to the first intravascular carrier 108A. For example, the first electrode array 102A may consist of 2 to 16 electrodes. In other embodiments, the first electrode array 102A may consist of 16 to 20 electrodes, or more than 20 electrodes.

[0058] The second electrode array 102B may consist of a plurality of electrodes 112 coupled to the second intravascular carrier 108B. For example, the second electrode array 102B may consist of 2 to 16 electrodes. In other embodiments, the second electrode array 102B may consist of 16 to 20 electrodes, or more than 20 electrodes.

[0059] If the electrode array 102 (for example, either the first electrode array 102A or the second electrode array 102B) is used to detect or record the electrophysiological signals of a subject, the electrode array may be called a recording electrode array. Furthermore, if the electrode array (for example, either the first electrode array 102A or the second electrode array 102B) is used to stimulate a target area within the subject's body, the electrode array may be called a stimulating electrode array.

[0060] In some embodiments (for example, the embodiment shown in Figure 1), the first intravascular carrier 108A and the second intravascular carrier 108B can be expandable stents or intravascular scaffolds. The intravascular carrier and the electrode array coupled to such carrier can be referred to as the stent-electrode array 109. The stent-electrode array 109 will be described in detail in a later section.

[0061] In other embodiments, at least one of the first intravascular carrier 108A and the second intravascular carrier 108B may be a biocompatible coiled wire 200 (see, for example, Figure 2A), a biocompatible anchored wire 208 (see, for example, Figure 2C), or a combination thereof.

[0062] In certain embodiments, the first intravascular carrier 108A may be the same as the second intravascular carrier 108B (for example, both the first intravascular carrier 108A and the second intravascular carrier 108B may be a stent-electrode array 109, a coiled wire 200, or an anchored wire 208). In other embodiments, the first intravascular carrier 108A may be different from the second intravascular carrier 108B (for example, the first intravascular carrier 108A may be a stent-electrode array 109, and the second intravascular carrier 108B may be a coiled wire 200).

[0063] Figure 1 shows a neuromodulatory system 100 comprising two electrode arrays 102 and two intravascular carriers 108, but it is intended by this disclosure that the neuromodulatory system 100 may consist of three to five electrode arrays 102 and intravascular carriers 108. In additional embodiments, the neuromodulatory system 100 may consist of five to ten electrode arrays 102 and intravascular carriers 108.

[0064] The neural modulator 104 may be configured to be implanted in the subject's body. In some embodiments, the neural modulator 104 may be configured to be implanted in the subject's forearm (see, for example, Figure 3B). In other embodiments, the neural modulator 104 may be configured to be implanted in the subject's chest region (see, for example, Figure 3A). The neural modulator 104 may also be implanted in, or configured to be implanted in, the subject's axillary region.

[0065] Each of the first electrode array 102A and the second electrode array 102B may be connected to the neuromodulatory unit 104 via one or more transmission leads 106 or lead wires. In some embodiments, the transmission leads 106 may be inserted into or connected to the header portion 114 of the neuromodulatory unit 104.

[0066] The header section 114 may consist of different plug receivers for leads or plugs coming from different electrode arrays. For example, the header section 114 may consist of a 0.9 mm plug receiver for receiving a plug or connector from a first transmission lead 106A connected to or coupled to a first electrode array 102A that functions as a recording electrode array, and a 1.3 mm plug receiver for receiving a plug or connector from a second transmission lead 106B connected to or coupled to a second electrode array 102B that functions as a stimulation electrode array.

[0067] The neural control unit 104 may consist of a unit housing 116. The unit housing 116 may be a sealed housing or enclosure such that the electronic components within the neural control unit 104 are enclosed within the unit housing 116. The unit housing 116 can be formed from a biocompatible material. For example, part of the unit housing 116 may be made from a metallic material (e.g., titanium, stainless steel, platinum, or a combination thereof), a polymeric material, or a combination thereof.

[0068] In some embodiments, the pulse generator 110 may be part of the neural modulator 104 or may be contained within the unit housing 116. In some embodiments, the portable neural modulator 104 may comprise one or more batteries (e.g., rechargeable or non-rechargeable batteries). In certain embodiments, the batteries of the neural modulator 104 may be rechargeable via wireless induction charging.

[0069] In other embodiments, the neural modulator 104 can be powered and / or operated by an external device 300 (see, for example, Figure 3A). The neural modulator 104 may include a first magnetic component 118, and the external device 300 may include a second magnetic component 302 (see, for example, Figure 3A) configured to be magnetically coupled to the first magnetic component 118. The neural modulator 104 including a pulse generator 110 may be configured to be charged via electromagnetic induction by the external device 300 or operated by the external device 300 when the external device 300 is placed near the neural modulator 104, such as by bringing the external device 300 close to the implantation site of the neural modulator 104. In these embodiments where the neural modulator 104 and the pulse generator 110 are the same device, any reference to the neural modulator 104 may also refer to the pulse generator 110.

[0070] In other embodiments, the pulse generator 110 may be a separate device or apparatus from the neural modulator 104. In these embodiments, the pulse generator 110 may be implanted in the subject's body, and the neural modulator 104 may be an extracorporeal unit that operates outside the subject's body. In these embodiments, the neural modulator 104 functions as an extracorporeal device 300 and is capable of processing data received wirelessly or via physical leads from a first electrode array 102A, a second electrode array 102B, or a combination thereof.

[0071] In further embodiments, the portable pulse generator 110 may comprise one or more batteries (e.g., rechargeable or non-rechargeable batteries). In certain embodiments, the batteries of the pulse generator 110 may be recharged via radio induction charging.

[0072] If the pulse generator 110 is a separate device implanted in the body of a subject (for example, implanted in the forearm, chest area, axilla, etc.), the pulse generator 110 can be powered and operated by an external device 300 (see, for example, Figure 3). In some embodiments, the pulse generator 110 may include a first magnetic component 118, and the external device 300 may include a second magnetic component 302 configured to be magnetically coupled to the first magnetic component 118. The pulse generator 110 may be configured to be charged by the external device 300 by electromagnetic induction when the external device 300 is positioned near the pulse generator 110, such as by bringing the external device 300 close to the implantation site of the pulse generator 110.

[0073] The neural modulation unit 104 may further include a telemetry unit 120 or a telemetry module (e.g., a telemetry hardware module, a telemetry software module, or a combination thereof). The telemetry unit 120 may be configured to analyze electrophysiological signals detected or recorded by the electrode array by comparing the electrophysiological signals with one or more predetermined signal thresholds or patterns. For example, the neural modulation unit 104 (or the telemetry unit 120 within the neural modulation unit 104) may consist of one or more processors and one or more memory units. One or more processors may be programmed to execute instructions stored in one or more memory units and compare the electrophysiological signals with one or more predetermined signal thresholds or patterns as part of the analysis.

[0074] In some embodiments, the electrophysiological signal may be local field potential (LFP) and / or intracranial / cortical EEG measured in the subject's brain using one of an electrode array implanted intravascularly within the subject's body (e.g., a first electrode array 102A, a second electrode array 102B, or a combination thereof). In other embodiments, the electrophysiological signal may be an intracranial or cortical electroencephalogram (EEG) signal.

[0075] In other embodiments, the electrophysiological signal may be an electrocortical (ECoG) signal received by the telemetry unit 120 from an ECoG electrode array deployed on the surface of the brain. For example, the ECoG electrode array may be a flexible or stretchable electrode mesh, or one or more electrode patches placed on the surface of the brain.

[0076] In further embodiments, the electrophysiological signal may be a signal indicating the subject's heart rate or a change in heart rate. For example, the electrophysiological signal may be an electrocardiogram (ECG / EKG) signal measured by the neuromodulator 104 when it is implanted in the subject's chest or subclavian space.

[0077] In certain embodiments, the electrophysiological signal may be an EEG signal received by the telemetry unit 120 from a plurality of external electrodes (external electrode array) placed on the subject's scalp. For example, the EEG signal may be obtained from an electroencephalogram monitoring system (e.g., an EEG skullcap or EEG visor) worn on the head. In these embodiments, the EEG electrodes may function as a recording or sensing electrode array.

[0078] Electrophysiological signals can provide information or data that can be used to predict or indicate whether an epileptic seizure is about to occur in a subject. For example, if the electrophysiological signal is an EEG signal, the neural control unit 104 can instruct the pulse generator 110 to generate an electrical impulse when an epileptic-like transient or other pre-seizure sign is detected in the EEG signal.

[0079] The neural modulator 104 (or telemetry unit 120) can adjust or change one or more signal thresholds. Furthermore, the neural modulator 104 can also select from different signal thresholds. For example, the neural modulator 104 can raise or lower the signal threshold based on the frequency with which the subject experiences seizures after the signal threshold is met (or not met).

[0080] The neural modulation system 100 is thought to operate in a closed-loop mode, or to perform “responsive nerve stimulation,” when stimulating a target site in the body in response to detected electrophysiological signals associated with or correlated with the onset of epileptic seizures. In some embodiments, the system 100 may also classify or stratify detected or recorded electrophysiological signals into low-risk, medium-risk, or high-risk categories and generate an electrical impulse only if the signal is considered medium-risk or high-risk.

[0081] The neural control unit 104 can be configured to analyze an electrophysiological signal detected or recorded by at least one of the electrode arrays (for example, the first electrode array 102A, the second electrode array 102B, or any combination thereof) and to transmit an electrical impulse to the same electrode array or another electrode array via the pulse generator 110 in response to the detected or recorded electrophysiological signal.

[0082] The electrical impulse can be biphasic, monophasic, sinusoidal, or a combination thereof. The pulse generator 110 can generate an electrical impulse by increasing the current amplitude of the electrical impulse from 0 mA to a maximum of 10 mA in increments of 0.1 mA, and by increasing the voltage of the electrical impulse from 0 V to a maximum of 10 V in increments of 0.25 V. The generated electrical impulse can have a pulse width of 25 μS to approximately 600 μS. Furthermore, different stimulation timing patterns can be enabled by adjusting the timing parameters of the electrical impulse.

[0083] The generated electrical impulses can have frequencies ranging from 1 Hz to 400 Hz. For example, the frequency of the electrical impulses can be set to low frequency (approximately 1 Hz to 10 Hz), medium frequency (approximately 10 Hz to 150 Hz), or high frequency (approximately 150 Hz to 400 Hz). By stimulating a target area in the body (such as the vagus nerve), it is possible to increase blood flow to major parts of the brain and raise the concentration of specific neurotransmitters involved in suppressing seizure activity (e.g., inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA)).

[0084] In other embodiments, the neural control system 100 can operate in an open-loop mode or configuration that intermittently or periodically stimulates a target site in the body via an electrode array based on a preset schedule.

[0085] Figures 2A to 2D illustrate various other embodiments of the intravascular carrier 108, which can be used to support the electrode array 102 and to fix the electrode array 102 to an implantation site within the vascular system of a subject.

[0086] As shown in Figure 1, the intravascular carrier 108 can be an expandable stent or intravascular scaffold, which includes an electrode array 102 coupled to the expandable stent or intravascular scaffold. The expandable stent or intravascular scaffold can consist of multiple filaments woven into a tubular structure.

[0087] In some embodiments, the stent or scaffold is configured to be self-expandable. For example, the stent or scaffold may self-expand from a collapsed or folded form to an expanded form when deployed in the vascular system of a subject. For example, the stent or scaffold may self-expand to a preset shape and diameter to fit a particular vein, artery, or other blood vessel. In other embodiments, the stent or scaffold may be expanded by a balloon catheter.

[0088] The electrodes 112 of the electrode array 102 may be attached, fixed, or otherwise coupled to the outer boundary or radially outer portion of the expandable stent or scaffold. For example, the electrodes 112 of the electrode array 102 may be positioned along the filaments that constitute the outer boundary or radially outer portion of the expandable stent or scaffold (i.e., the portion of the stent or scaffold configured to contact the vascular lumen).

[0089] In some embodiments, the filaments of an expandable stent or intravascular scaffold may be partially formed from a shape memory alloy. For example, a portion of the filaments of an expandable stent or intravascular scaffold can be formed from nitinol (e.g., nitinol wire). Alternatively, a portion of the filaments of an expandable stent or intravascular scaffold can be formed from stainless steel, gold, platinum, nickel, titanium, tungsten, aluminum, nickel-chromium alloy, gold-palladium-rhodium alloy, chromium-nickel-molybdenum alloy, iridium, rhodium, or a combination thereof. Furthermore, a portion of the filaments of an expandable stent or intravascular scaffold can also be formed from a shape memory polymer.

[0090] When the intravascular carrier 108 is an expandable stent or intravascular scaffold supporting the electrode array 102, the entire carrier and array assembly can be referred to as the stent-electrode array 109.

[0091] The stent-electrode array 109 disclosed herein is described in U.S. Patent Publication No. 2014 / 0288667, U.S. Patent Publication No. 2020 / 0078195, U.S. Patent Publication No. 2019 / 0336748, U.S. Patent Publication No. 2020 / 0016396, U.S. Patent No. 10,575,783, U.S. Patent No. 10,485,968, U.S. Patent No. 10,729,530, U.S. Patent No. 10,512,555, U.S. Patent Application No. 16 / 457,493 filed on 28 June 2019, U.S. Patent Application No. 62 / 927,574 filed on 29 October 2019, and U.S. Patent Application No. 62 / 932,906 filed on 8 November 2019. Any stent, scaffold, stent electrode, or stent electrode array disclosed in the following specifications, U.S. Patent Application No. 62 / 932,935 filed on November 8, 2019, U.S. Patent Application No. 62 / 935,901 filed on November 15, 2019, U.S. Patent Application No. 62 / 941,317 filed on November 27, 2019, U.S. Patent Application No. 62 / 950,629 filed on December 19, 2019, U.S. Patent Application No. 63 / 003,480 filed on April 1, 2020, and U.S. Patent Application No. 63 / 057,379 filed on July 28, 2020, the contents of which are disclosed in their entirety by reference herein.

[0092] Figure 2A shows an example of an intravascular carrier 108 as a coiled wire 200. The coiled wire 200 can be used in blood vessels that are too small to accommodate a stent-electrode array 109.

[0093] The coiled wire 200 can be a biocompatible wire 202 or microwire configured to be wound into a coiled pattern or substantially helical pattern. The electrodes 112 of the electrode array 102 can be interspersed along the length of the coiled wire 200. More specifically, the electrodes 112 of the electrode array 102 can be attached, fixed, or otherwise bonded to distinct points along the length of the coiled wire 200. The electrodes 112 of the electrode array 102 can be separated from each other such that no two electrodes 112 are within a predetermined separation distance from each other (e.g., at least 10 μm, at least 100 μm, or at least 1.0 mm).

[0094] In some embodiments, the wire 202 or microwire may be configured to automatically wind itself into a coiled shape (e.g., a spiral pattern) when the wire 202 or microwire is deployed from the delivery catheter. For example, a coiled wire 200 may automatically assume its coiled shape by shape memory when the delivery catheter or sheath is stored. The coiled shape or form may be a preset shape or shape-memory shape of the wire 202 or microwire prior to its introduction into the delivery catheter. The preset or pre-formed shape may be larger than the expected diameter of the deployment or grafting vessel so that the radial force exerted by the coil can fix or position the coiled wire 200 in a predetermined position within the deployment or grafting vessel.

[0095] In other embodiments, the coiled wire 200 can achieve a coiled shape when a pressing force is applied to the wire 202 or microwire in order to force or otherwise bias the wire 202 or microwire into a coiled shape.

[0096] As shown in Figure 2A, the coiled wire 200 may have a wire diameter 204 and a coil diameter 206. The wire diameter 204 may be the diameter of the base wire 202 or microwire used to form the intravascular carrier 108. In some embodiments, the wire diameter 204 may be about 25 μm to about 1.0 mm. In other embodiments, the wire diameter 204 may be about 100 μm to about 500 μm.

[0097] The coil diameter 206 can be 1.0 mm to 15.0 mm. More specifically, the coil diameter 206 can be approximately 3.0 mm to approximately 8.0 mm (for example, approximately 6.0 mm or approximately 7.0 mm). In some embodiments, the coil diameter 206 can be 15.0 mm to approximately 25.0 mm. The coil diameter 206 can be set based on the diameter of the target blood vessel or the vessel to be exposed.

[0098] Wire 202 or microwire can be formed in part from shape memory alloys, shape memory polymers, or combinations thereof. For example, wire 202 or microwire can be made in part from nitinol (e.g., nitinol wire). Furthermore, wire 202 or microwire can be formed from stainless steel, gold, platinum, nickel, titanium, tungsten, aluminum, nickel-chromium alloys, gold-palladium-rhodium alloys, chromium-nickel-molybdenum alloys, iridium, rhodium, or combinations thereof.

[0099] Figure 2B illustrates that a first electrode array 102A may be supported by a first coiled wire 200A, and a second electrode array 102B may be supported by a second coiled wire 200B connected to the first coiled wire 200A. In this embodiment, the first coiled wire 200A can function as a first intravascular carrier 108A, and the second coiled wire 200B can function as a second intravascular carrier 108B. Each of the first coiled wire 200A and the second coiled wire 200B can be the same as the coiled wire 200 (see Figure 2A) described earlier.

[0100] The first coiled wire 200A may be connected to the second coiled wire 200B by a non-coiled segment of wire 202 or a microwire. For example, the first coiled wire 200A may be connected to the second coiled wire 200B by a non-coiled segment of wire 202 or a microwire that was used to form the first coiled wire 200A and the second coiled wire 200B.

[0101] As will be described in more detail in a later section, the first coiled wire 200A, which functions as the first intravascular carrier 108A, and the second coiled wire 200B, which functions as the second intravascular carrier 108B, can be implanted along different sections of the same vessel or within different vessels.

[0102] In some embodiments, a first electrode array 102A supported by a first coiled wire 200A may function as a recording electrode array, and a second electrode array 102B supported by a second coiled wire 200B may function as a stimulation electrode array. In other embodiments, both the first electrode array 102A supported by the first coiled wire 200A and the second electrode array 102B supported by the second coiled wire 200B may function as at least one of a recording electrode array and a stimulation electrode array.

[0103] Figure 2C shows an intravascular carrier 108 according to a further embodiment as an anchored wire 208. The anchored wire 208 can be used in blood vessels that are too small or too tortuous to accommodate either the coiled wire 200 or the stent-electrode array 109.

[0104] The anchored wire 208 may consist of a biocompatible wire 202 or microwire attached to an anchor or another type of intravascular fixation mechanism, or otherwise joined.

[0105] Figure 2C shows that the anchored wire 208 may consist of a barbed anchor 210, a radially expandable anchor 212, or a combination thereof (both the barbed anchor 210 and the radially expandable anchor 212 are shown as dashed or dotted lines in Figure 2C).

[0106] In some embodiments, the barbed anchor 210 may be positioned at the distal end of the anchored wire 208. In other embodiments, the barbed anchor 210 may be positioned along one or more sides of the wire 202 or microwire. The barbs of the barbed anchor 210 can fix or anchor the anchored wire 208 to the implantation site in the subject's body.

[0107] The radially expandable anchor 212 may be a section of wire 202 or microwire formed as a coil or loop. The coil or loop may be sized so that it conforms to the vascular lumen and expands against the luminal wall to secure the anchored wire 208 to the implantation site within the vessel. For example, the coil or loop may be sized larger than the expected diameter of the deployed or implanted vessel so that the radial force applied by the coil or loop can secure or position the anchored wire 208 in place within the implanted vessel.

[0108] In some embodiments, the radially expandable anchor 212 may be positioned at the distal end of the anchored wire 208. In other embodiments, the radially expandable anchor 212 may be positioned along the proximal section of the distal end of the anchored wire 208.

[0109] The electrodes 112 of the electrode array 102 can be scattered along the length of the coiled wire 200. More specifically, the electrodes 112 of the electrode array 102 can be attached, fixed, or otherwise joined to distinct points along the length of the anchored wire 208. The electrodes 112 of the electrode array 102 can be separated from each other such that no two electrodes 112 are within a predetermined separation distance from each other (e.g., at least 10 μm, at least 100 μm, or at least 1.0 mm).

[0110] Figure 2C illustrates an anchored wire 208 having only one barbed anchor 210 and one radially expandable anchor 212, but it is intended by this disclosure that the anchored wire 208 may consist of multiple barbed anchors 210 and / or multiple radially expandable anchors 212.

[0111] Figure 2D shows an intravascular carrier 214 according to one embodiment, which supports different electrode arrays 102 (for example, a first electrode array 102A and a second electrode array 102B). As shown in Figure 2D, the intravascular carrier 214 can be the stent-electrode array 109 described earlier.

[0112] In this embodiment, two electrode arrays 102 may be coupled to the same expandable stent or intravascular scaffold. In other embodiments, three or more electrode arrays 102 may be coupled to the same expandable stent or intravascular scaffold.

[0113] In Figure 2D, the electrodes 112 of the first electrode array 102A are shown with black circles, and the electrodes 112 of the second electrode array 102B are shown with white circles. However, those skilled in the art will understand that the difference in color is solely for the purpose of making the illustration easier.

[0114] The electrodes 112 of the first electrode array 102A can be used as dedicated recording electrodes or sensing electrodes, and the electrodes 112 of the second electrode array 102B can be used as dedicated stimulating electrodes. In this way, only one intravascular carrier is required to deploy both the recording electrode array and the stimulating electrode array. Furthermore, in this embodiment, the electrodes 112 of the first electrode array 102A can record and communicate via a different data channel or communication channel than those of the electrodes 112 of the second electrode array 102B.

[0115] Figure 2D illustrates the intravascular carrier 214 as an expandable stent or scaffold, but it is intended by this disclosure that any of the intravascular carriers disclosed herein, including the coiled wire 200 and the anchored wire 208, can be used as an intravascular carrier for supporting at least two types of electrode arrays 102.

[0116] The electrodes 112 of the electrode array 102 depicted in Figures 2A to 2D can be formed in part from platinum, platinum black, another precious metal, or an alloy or composite thereof. For example, the electrodes 112 of the electrode array 102 can be formed from gold, iridium, palladium, a gold-palladium-rhodium alloy, rhodium, or a combination thereof. In some embodiments, the electrodes 112 can be formed from a metal composite (e.g., a platinum-iridium alloy or composite) having a high charge implantation capacity.

[0117] In some embodiments, the electrode 112 may be formed as a circular disk having a disk diameter of about 100 μm to 1.0 mm. In other embodiments, the electrode 112 may have a disk diameter of 1.0 mm to 1.5 mm. In additional embodiments, the electrode 112 may be cylindrical, spherical, cuff-shaped, ring-shaped, partially ring-shaped (e.g., C-shaped), or semi-cylindrical.

[0118] The conductivity of electrode 112 can be increased by increasing its surface area through surface roughening by chemical or electrochemical roughening methods, or by coating with a conductive polymer coating such as poly(3,4-ethylenedioxythiophene)polystyrene sulfonic acid (PEDOT:PSS).

[0119] Figure 3A shows that the neural modulator 104 and the intravascular carrier 108 supporting the electrode array 102 can be implanted in the body of a subject. In some embodiments, the neural modulator 104 can be powered by a portable power source such as one or more rechargeable batteries. In these embodiments and other embodiments, the batteries of the neural modulator 104 can be charged by an external device 300 via electromagnetic induction. In some embodiments, the external device 300 can also operate or power the neural modulator 104 when it is positioned near the neural modulator 104 (for example, when it is placed next to the implantation site of the neural modulator 104).

[0120] For example, the neural modulation unit 104 may consist of a first magnetic component 118 (e.g., a receiving coil or a secondary coil), and the external device 300 may consist of a second magnetic component 302 (e.g., a primary coil or a transmitting coil) configured to be magnetically coupled to the first magnetic component 118. The external device 300 can charge or power the neural modulation unit 104 by electromagnetic induction.

[0121] In some embodiments, the pulse generator 110 can be a standalone device separate from the nerve modulator 104. In these embodiments, the pulse generator 110 may also consist of a first magnetic component 118 (e.g., a receiving coil or a secondary coil) configured to be magnetically coupled to a second magnetic component 302 (e.g., a primary coil or a transmitting coil) within the external device 300. In these embodiments, the pulse generator 110 can be charged or powered by the external device 300 via electromagnetic induction.

[0122] As shown in Figure 3A, any of the intravascular carriers 108 can be implanted in the cortical or cerebral blood vessels of the subject. For example, an electrode array 102 coupled to a stent-electrode array 109 functioning as an intravascular carrier 108 can be implanted in the subject's venous sinus (e.g., superior sagittal sinus). The stent-electrode array 109 can be directly connected to or coupled to the neuromodulatory unit 104 via its own transmission leads 106 or cables. In other embodiments, the stent-electrode array 109 can be coupled to the neuromodulatory unit 104 via shared transmission leads 106 or cables.

[0123] In some embodiments, the stent-electrode array 109 deployed in the venous sinus may be used to detect or record the subject's electrophysiological signals (i.e., used as a recording electrode array). In other embodiments, the stent-electrode array 109 deployed in the venous sinus may be used to stimulate a target area in the subject's body (e.g., the motor cortex). Thus, the stent-electrode array 109 deployed in the venous sinus may be used as a stimulation electrode array. In further embodiments, the stent-electrode array 109 deployed in the venous sinus may be used as both a recording electrode array and a stimulation electrode array (see, for example, the stent-electrode array in Figure 2D).

[0124] Figure 3A also illustrates that an electrode array 102 coupled to a coiled wire 200, which functions as an intravascular carrier 108, may be implanted in a subject's superficial cerebral vein (e.g., Trollado's vein). The coiled wire 200 may be directly connected to or coupled to the neuromodulatory unit 104 via its own transmission leads 106 or cables. In other embodiments, the coiled wire 200 may be coupled to the neuromodulatory unit 104 via shared transmission leads 106 or cables.

[0125] In some embodiments, the coiled wire 200 deployed in the superficial cerebral veins can be used to detect or record the electrophysiological signals of a subject (i.e., used as a recording electrode array). In other embodiments, the coiled wire 200 deployed in the superficial cerebral veins can be used to stimulate a target area in the subject's body (e.g., the motor cortex). Thus, the coiled wire 200 deployed in the superficial cerebral veins can be used as a stimulation electrode array. In further embodiments, the coiled wire 200 deployed in the superficial cerebral veins can be used as both a recording electrode array and a stimulation electrode array.

[0126] Figure 3A further illustrates that an electrode array 102 coupled to an anchored wire 208, which functions as an intravascular carrier 108, may be implanted in a subject's deep cerebral vein (e.g., superior thalamostriate vein). The anchored wire 208 may be directly connected to or coupled to the neuromodulatory unit 104 via its own transmission leads 106 or cables. In other embodiments, the anchored wire 208 may be coupled to the neuromodulatory unit 104 via shared transmission leads 106 or cables.

[0127] In some embodiments, the anchored wire 208 deployed in the deep cerebral vein can be used to detect or record the electrophysiological signals of a subject (i.e., used as a recording electrode array). In other embodiments, the anchored wire 208 deployed in the deep cerebral vein can be used to stimulate a target area in the subject's body (e.g., the anterior nucleus thalamus). Thus, the anchored wire 208 deployed in the deep cerebral vein can be used as a stimulation electrode array. In further embodiments, the anchored wire 208 deployed in the deep cerebral vein can be used as both a recording electrode array and a stimulation electrode array.

[0128] Figure 3A further illustrates that the electrode array 102 coupled to the stent-electrode array 109, which functions as an intravascular carrier 108, may be implanted in the internal jugular vein above (or above) the jugular foramen of the subject. In some embodiments, the entire stent-electrode array 109 may be implanted in the internal jugular vein above the jugular foramen.

[0129] In some embodiments, at least a portion of the stent-electrode array 109 may be implanted in the internal jugular vein superior to the jugular foramen. Implantation of the stent-electrode array 109 superior to the jugular foramen will be described in detail in a later section.

[0130] In some embodiments, the stent-electrode array 109 implanted in the internal jugular vein can be used to stimulate a target site in the subject's body (e.g., the superior ganglion of the vagus nerve). Thus, the stent-electrode array 109 implanted in the internal jugular vein can be used as a stimulating electrode array.

[0131] Figure 3A further illustrates that an electrode array 102 coupled to an intravascular carrier 108 (e.g., a coiled wire 200, a stent-electrode array 109, or an anchored wire 208) can be used as a recording electrode array to record electrophysiological signals indicating the subject's heart rate or changes in heart rate (e.g., paroxysmal tachycardia). These electrocardiogram signals may be associated with or correlated with the onset of an epileptic seizure. For example, these electrophysiological signals may be cardiac arrhythmias, which are well known to be associated with or correlated with a high likelihood of developing an epileptic seizure.

[0132] As shown in Figure 3A, the neural modulatory unit 104 can be implanted below the head and neck of the subject. For example, as shown in Figure 3A, the neural modulatory unit 104 can be implanted within the thoracic region of the subject (e.g., below the pectoralis major muscle).

[0133] As described above, in some embodiments, the pulse generator 110 can be part of the nerve modulator 104. In other embodiments, the pulse generator 110 can be a standalone device separate from the nerve modulator 104. In these embodiments, the pulse generator 110 can be implanted in the chest region of the subject (for example, beneath the pectoralis major muscle).

[0134] Figure 3B illustrates that the neural modulator 104 may be implanted in the forearm of a subject. In this embodiment, the neural modulator system 100 may consist of an external device 300 in the form of an armband 308. The implantable neural modulator 104 may consist of a first magnetic component 118 (e.g., a receiving coil or a secondary coil), and the armband 308 may consist of a second magnetic component 302 (e.g., a primary coil or a transmitting coil). The armband 308 can charge or power the neural modulator 104 by electromagnetic induction.

[0135] As described above, in some embodiments, the pulse generator 110 can be a standalone device separate from the nerve modulator 104. In these embodiments, the pulse generator 110 can be implanted in the forearm of the subject. The pulse generator 110 can consist of a first magnetic component 118 (e.g., a receiving coil or a secondary coil), and the armband 308, which functions as an external device 300, can consist of a second magnetic component 302 (e.g., a primary coil or a transmitting coil). The armband 308 can charge or power the pulse generator 110 by electromagnetic induction.

[0136] Figure 3A further illustrates that the external device 300 can also be implemented as a portable handheld device 304, a wand 306, or a wearable device 308 (e.g., a bracelet or wristwatch). The external device 300 can be used to recharge one or more batteries of the neural modulator 104, the pulse generator 110, or a combination thereof. In some embodiments, the external device 300 can be used to activate the pulse generator 110 to transmit electrical impulses to the stimulation electrode array.

[0137] Figures 4A to 4C illustrate a transmission lead 106 according to one embodiment used to connect the electrode array 102 to the neural control unit 104, the pulse generator 110, or a combination thereof. For example, the transmission lead 106 can be used to connect the first electrode array 102A or the second electrode array 102B to the neural control unit 104, the pulse generator 110, or a combination thereof.

[0138] As shown in Figures 4A to 4C, the transmission lead 106 may include at least one variable-length section 400 between the intravascular carrier 108 and the transmission section 402. The section length 404 of the variable-length section 400 can be adjusted (e.g., shortened or lengthened) after the transmission lead 106 has been deployed in the subject's body blood vessels (e.g., veins, arteries, or sinuses).

[0139] The transmission section 402 may be a proximal portion of a transmission lead 106 configured to connect to or plug into the neural modulator 104 (for example, to the header 114 of the neural modulator 104). The transmission section 402 may be formed from one or more conductive wires without shape memory. For example, a portion of the transmission section 402 may be formed from a platinum wire or a platinum-iridium wire. The transmission section 402, along with other portions of the transmission lead 106, may be covered with an insulator (e.g., polyurethane) or an insulating coating.

[0140] Figures 4A to 4C illustrate that the variable length portion 400 may be connected to or coupled to the proximal end of the intravascular carrier 108. For example, the intravascular carrier 108 may be a coiled wire 200, and the variable length portion 400 may be directly connected to or coupled to the proximal end of the coiled wire 200.

[0141] The variable-length portion 400 of the transmission lead 106 can be formed in part from a shape memory alloy. Alternatively, the variable-length portion 400 of the transmission lead 106 can be formed from a composite material consisting of a shape memory alloy. For example, the variable-length portion 400 of the transmission lead 106 can be formed in part from nitinol (e.g., nitinol wire). In some embodiments, the variable-length portion 400 of the transmission lead 106 can be formed from a composite clad wire or a nitinol wire having a conductive (e.g., gold or platinum) wire core.

[0142] Figure 4A illustrates the shape of the coiled wire 200 and transmission lead 106 when they are retracted within the delivery catheter or sheath. Figure 4B illustrates the shape of the coiled wire 200 and transmission lead 106 when they are unfolded from the delivery catheter or when the delivery catheter or sheath is retracted.

[0143] As shown in Figure 4B, the variable length portion 400 of the transmission lead 106 may be configured to automatically recover a preset or pre-fabricated shape. In some embodiments, the preset or pre-fabricated shape may be a loosely wound coil, i.e., a coiled shape having a larger pitch or fewer turns than the coil of the coiled wire 200. The variable length portion 400 can automatically return to its loosely wound shape by shape memory when the delivery catheter or sheath carrying the variable length portion 400 is retracted.

[0144] In certain embodiments, the pre-set or pre-tailored shape of the coil formed by the variable length section 400 may have a coil diameter less than, i.e., smaller than, the diameter of the expected deployed or implanted blood vessel. This ensures that the radial force exerted by the coil on the vascular lumen wall does not prevent the coil of the variable length section 400 from moving, contracting, or expanding within the blood vessels of the subject. In some embodiments, this contraction and expansion can change the section length 404 of the variable length section 400 (e.g., shortening or lengthening). For example, the variable length section 400 can be lengthened by stretching the proximal (or distal) end of the variable length section 400. The variable length section 400 can be shortened by pressing the proximal end of the variable length section 400 when the intravascular carrier 108, which is attached to the distal end of the variable length section 400, is implanted in, or otherwise fixed within, the deployed blood vessel. The variable length portion 400 can also be shortened by pressing its distal end when the intravascular carrier 108, which is attached to the proximal end of the variable length portion 400, is implanted into the unfolding blood vessel or otherwise fixed in place.

[0145] In some embodiments, the variable length portion 400 can become coiled only when or only when a pressing force is applied to the variable length portion 400 to force or bias it into a coiled shape.

[0146] In a further embodiment, the variable length portion 400 may be a section of the transmission lead 106 that has little or no shape memory and is configured to wrap around or deform when a pressing force is applied to the variable length portion 400.

[0147] One of the technical challenges faced by the applicants is how to design an implantable neuromodulatory system that includes endovascular carriers connected or coupled by transmission leads when the distance between endovascular carriers or the distance between endovascular carriers and implantable neuromodulators or pulse generators varies depending on the patient or treatment regimen. For example, the length of the neck and torso varies among subjects, and the location in each subject where such endovascular carriers are implanted requires a neuromodulatory system that can adapt to different anatomical and implantation requirements. One advantage of the neuromodulatory system 100 disclosed herein lies in the unique transmission lead 106, comprising a variable-length section 400 disclosed herein, which allows the neuromodulatory system 100 to be adapted to patients of different sizes and patients with different implantation requirements.

[0148] In some embodiments, the transmission lead 106 may have a lead diameter of 0.5 mm to 1.5 mm. More specifically, the transmission lead 106 may have a lead diameter of 0.5 mm to 1.0 mm.

[0149] In some embodiments, the transmission lead 106 or its section may be covered with an insulator or insulating coating. For example, the transmission lead 106 or its section may be covered with polyurethane or a polyurethane coating.

[0150] In some embodiments, at least one section of the transmission lead 106 may be a cable consisting of multiple conductive wires or transmission wires coupled to various electrodes 112 of the electrode array 102. For example, the transmission lead 106 may be a stranded cable in which multiple conductive wires are twisted together and bundled, and covered with an insulator or insulating material.

[0151] Figures 5A to 5C show an example of a method for implanting an electrode array 102 (for example, either a first electrode array 102A or a second electrode array 102B) according to one embodiment. This method can be used when the target site 500 in the body is near, but not adjacent to, a blood vessel 502 used to deliver or deploy the electrode array 102.

[0152] As shown in Figures 5A and 5B, when the delivery catheter 504 is moved to a position near the vessel wall 506, the intravascular carrier 108 carrying the electrode array 102 can be deployed from the delivery catheter 504. In the embodiments shown in Figures 5A to 5C, the intravascular carrier 108 may be an anchored wire 208 having the electrode array 102 coupled along a biocompatible wire 202 or microwire section (see also Figure 2C).

[0153] The wire 202 or microwire may include a sharp distal end in the form of a penetrating barb 508 or penetrating anchor that is coupled or detachably coupled to the distal end of the wire 202 or microwire. The penetrating barb 508 or penetrating anchor allows the wire 202 or microwire to penetrate the vessel wall 506 or to form a perforation in the vessel wall 506, so that the wire 202 or microwire can extend through the vessel wall 506. The wire 202 or microwire can then be oriented to be closer to the target site 500 in the body (e.g., a target nerve site or brain site) so that the electrode array 102 is located in or very close to the target site 500 in the body.

[0154] Figure 5C illustrates that once the delivery catheter 504 is retracted, the wire portion 510 on the proximal side of the electrode array 102 can automatically take on a coil shape. The coil shape of the wire portion 510 can be preset prior to its introduction into the delivery catheter 504. For example, the wire portion 510 may have a lead diameter of approximately 1.0 mm (or less than 1.0 mm), and the blood vessel 502 may have a vessel diameter of approximately 6.0 mm. Once the delivery catheter 504 is removed, the wire portion 510 can take on a coil shape with a coil diameter greater than 6.0 mm. The wire portion 510 can self-expand until the coil is pressed against the internal blood vessel wall and fixed to the internal blood vessel wall. In this embodiment, the wire portion 510 on the proximal side of the electrode array 102 may also be used to fix the intravascular carrier 108. With the wire portion 510 and electrode array 102 in place, the penetrating barb 508 can be removed by a stylet or other device extending through the delivery catheter 504.

[0155] Figure 6 illustrates a method 600 for treating epilepsy according to one embodiment. Method 600 may include, in step 602, detecting the subject's electrophysiological signals using a first electrode array 102A. Thus, the first electrode array 102A can function as a recording electrode array. The first electrode array 102A can be attached, fixed, or bonded to a first intravascular carrier 108A (for example, spaced along the length of the first intravascular carrier 108A and / or bonded to the radially lateral portion of the first intravascular carrier 108A). The first intravascular carrier 108A can be implanted in the subject's artery, vein, or sinus. Possible implantation sites for the first intravascular carrier 108A are described in more detail in the following sections.

[0156] Method 600 may further include, in step 604, analyzing electrophysiological signals using a neural modulator 104 implanted in the body of a subject and electrically coupled to a first electrode array 102A via one or more conductive leads and / or transmission leads 106. The neural modulator 104 can be configured to analyze electrophysiological signals by (i) comparing detected signals against one or more thresholds (e.g., detecting signal spikes), (ii) detecting specific signal patterns or rhythmic activity in a particular frequency range, (iii) comparing absolute inter-sample amplitude differences within a given time window, (iv) measuring changes in signal energy, or a combination thereof.

[0157] Method 600 may further include stimulating a site of interest within the subject's body using a second electrode array 102B in response to the electrophysiological signal detected in step 606. Thus, the second electrode array 102B can function as a stimulating electrode array. The second electrode array 102B may be attached to, fixed to, or bonded to a second intravascular carrier 108B (for example, spaced along the length of the second intravascular carrier 108B and / or bonded to the radially lateral portion of the second intravascular carrier 108B). The second intravascular carrier 108B may be implanted in the subject's arteries, veins, or sinuses above the base of the subject's skull.

[0158] Figure 7 illustrates a method 700 for treating epilepsy in an alternative example. Method 700 may include, in step 702, detecting the subject's electrophysiological signals using a first electrode array 102A. Thus, the first electrode array 102A can function as a recording electrode array. The first electrode array 102A may be attached, fixed, or otherwise coupled to an intravascular carrier 108 implanted intravascularly in the subject's artery, vein, or sinus above the base of the subject's skull. For example, the intravascular carrier 108 may be the intravascular carrier 214 depicted in Figure 2D.

[0159] The first electrode array 102A is spaced along the length of the intravascular carrier 108 and / or can be coupled to the radially outer portion of the intravascular carrier 108. Possible implantation sites for the intravascular carrier 108 are described in more detail in the following sections.

[0160] Method 700 may further include, in step 704, analyzing electrophysiological signals using a neural modulator 104 implanted in the body of a subject and electrically coupled to a first electrode array 102A via one or more conductive leads and / or transmission leads 106. The neural modulator 104 can be configured to analyze electrophysiological signals by (i) comparing detected signals against one or more thresholds (e.g., detecting signal spikes), (ii) detecting specific signal patterns or rhythmic activity in a particular frequency range, (iii) comparing absolute inter-sample amplitude differences within a given time window, (iv) measuring changes in signal energy, or a combination thereof.

[0161] Method 700 may further include stimulating a target site in the subject's body using a second electrode array 102B in response to the electrophysiological signal detected in step 706. The second electrode array 102B may be spaced along the length of the intravascular carrier 108 and / or coupled to the radially outer portion of the intravascular carrier 108. Thus, the second electrode array 102B can function as a stimulating electrode array. The second electrode array 102B may be attached to, fixed to, or coupled to the same intravascular carrier 108 (for example, spaced along the length of the intravascular carrier 108 and / or coupled to the radially outer portion of the intravascular carrier 108). The electrodes of the second electrode array 102B may be separate from the electrodes of the first electrode array 102A.

[0162] Figures 6 and 7 disclose a method for treating epilepsy, but this disclosure intends that the neuromodulatory system 100 disclosed herein may also be used for treating other disorders or conditions, including headache, bipolar disorder, obesity, Alzheimer's disease, Parkinson's disease, rheumatoid arthritis, or inflammatory bowel disease. For example, a method for treating one of the above-mentioned conditions / disorders may include using a first electrode array 102A to detect electrophysiological signals of a subject associated with or related to the onset of symptoms associated with the condition / disorder. The first electrode array 102A may be coupled to a first intravascular carrier 108A implanted above the base of the subject's skull. The method may further include analyzing the electrophysiological signals using a neuromodulatory unit 104 that is electrically coupled to the first electrode array 102A and implanted in the subject's body. The method may further include stimulating a site of interest in the subject's body using a second electrode array 102B in response to the detected electrophysiological signals. The second electrode array 102B can be coupled to a second intravascular carrier 108B implanted intravascularly in the subject's body and electrically coupled to the neuromodulator 104. For example, stimulating a target site in the body may include generating electrical impulses using the pulse generator 110 of the neuromodulator 104. Stimulating a target site in the body may alleviate or reduce the symptoms or causes of a symptom / disorder.

[0163] Figure 8A illustrates that an endovascular carrier 108 (including either the first endovascular carrier 108A or the second endovascular carrier 108B) may be implanted in the internal jugular vein 800 (e.g., the right or left internal jugular vein) superior to the subject's jugular foramen 802. The jugular foramen 802 is a cavity formed inferior to the base of the subject's skull. The jugular foramen 802 is formed anteriorly by the petrous portion of the temporal bone and posteriorly by the occipital bone.

[0164] When the endovascular carrier 108 is implanted in the internal jugular vein 800 above the jugular foramen 802, the electrode array 102 coupled to the endovascular carrier 108 can be used to stimulate the subject's vagus nerve 804. In certain embodiments, the target site in the body or the site to be stimulated may be the superior ganglion 806 of the vagus nerve 804. In other embodiments, the target site in the body or the site to be stimulated may be both the superior ganglion 806 and the inferior ganglion 808 of the vagus nerve 804.

[0165] In some embodiments, a method for treating epilepsy may include implanting a first electrode array 102A, coupled to a first intravascular carrier 108A, into a subject's cerebral vein or cortical vein or sinus to record the subject's electrophysiological signals associated with, correlated with, or indicating the onset of an epileptic seizure. The method may also include implanting a second electrode array 102B, coupled to a second intravascular carrier 108B (e.g., a stent-electrode array 109), into the internal jugular vein 800 above the jugular foramen 802 to stimulate the subject's vagus nerve 804. A neuromodulator 104 electrically coupled to the first electrode array 102A and the second electrode array 102B can analyze the electrophysiological signals and instruct a pulse generator 110 of the neuromodulator 104 to generate electrical impulses to stimulate the vagus nerve 804.

[0166] The electrical impulse can be biphasic, monophasic, sinusoidal, or a combination thereof. For example, the electrical impulse can be a charge-balanced biphasic pulse. The pulse generator 110 can generate an electrical impulse by increasing the current amplitude of the electrical impulse from 0.25 mA to a maximum of 2 mA in 0.1 mA increments and by increasing the voltage of the electrical impulse from 0 V to a maximum of 10 V in 0.25 V increments. The generated electrical impulse may have a pulse width of 250 μS to approximately 500 μS. Furthermore, the stimulation timing pattern can be changed by adjusting the timing parameters of the electrical impulse. The generated electrical impulse may have a frequency of 10 Hz to 30 Hz.

[0167] In some embodiments, at least a portion of the endovascular carrier 108 may be implanted in the internal jugular vein 800 above the jugular foramen 802. In additional embodiments, at least a portion of the endovascular carrier 108 may be implanted in a branch or tributary of the internal jugular vein 800.

[0168] In additional embodiments, the endovascular carrier 108 may be implanted in the internal carotid artery 810 above the base of the subject's skull. In further embodiments, the endovascular carrier 108 may be implanted in the internal carotid artery 810 above the carotid foramen 812 of the subject. In other embodiments, at least a portion of the endovascular carrier 108 may be implanted in the internal carotid artery 810 above the base of the subject's skull. In further embodiments, at least a portion of the endovascular carrier 108 may be implanted in the internal carotid artery 810 above the carotid foramen 812. In these and other embodiments, the target site in the body may be the subject's vagus nerve 804.

[0169] Figure 8A illustrates the intravascular carrier 108 as a stent-electrode array 109, but this disclosure intends that any of the intravascular carriers 108 disclosed herein (including the coiled wire 200 or the anchored wire 208) can be implanted in the internal jugular vein 800. Furthermore, any of the intravascular carriers 108 disclosed herein (including the stent-electrode array 109, the coiled wire 200, or the anchored wire 208) can be implanted in the internal carotid artery 810.

[0170] Figures 8B and 8C illustrate an embodiment in which the vagus nerve 804 is located near the internal jugular vein 800. In most subjects, at least a portion of the vagus nerve 804 extending through the subject's neck to the skull is in contact with or adjacent to the internal jugular vein 800 (i.e., less than 2.0 mm away from the internal jugular vein 800).

[0171] For example, Figure 8B is a partial cross-sectional view of a subject at the level of the C6 vertebra, showing the surrounding blood vessels including the vagus nerve 804 and the internal jugular vein 800. As described above, the internal jugular vein 800 can serve as a possible implantation site for an intravascular carrier 108 that carries an electrode array 102 (e.g., a stimulating electrode array).

[0172] In some embodiments not shown, the intravascular carrier 108 may also be implanted in the common carotid artery (outside the subject's skull) or the external carotid artery.

[0173] One technical challenge faced by the applicant is that the endovascular carrier 108, implanted in the blood vessels within the subject's neck, can wear down over time as a result of natural neck movements (e.g., bending, flexing, stretching, and rotation). Furthermore, the endovascular carrier 108 implanted in the blood vessels within the neck can also be damaged by external forces applied to the subject's neck. One advantage of implanting the endovascular carrier 108 within the subject's skull (e.g., within the internal carotid artery above the jugular foramen) is that the skull acts as a protective housing for the endovascular carrier 108, with only one or more thin transmission leads 106 extending through the subject's neck. This also enhances patient comfort and extends the lifespan of the deployed endovascular carrier. Additionally, electrophysiological recordings from electrodes within the skull are less susceptible to external signals such as heart rate artifacts.

[0174] Figures 9A to 9G illustrate specific veins and sinuses in a subject that could function as implantation sites for intravascular carriers 108 bearing the electrode array 102. Furthermore, Figures 9A to 9G also illustrate specific sites of interest or sites of interest within the body that can be stimulated as part of the treatment of epilepsy or other disorders / symptoms.

[0175] In some embodiments, the first intravascular carrier 108A carrying the first electrode array 102A can be implanted in the subject's venous sinus. For example, the first intravascular carrier 108A carrying the first electrode array 102A can be implanted in the superior sagittal sinus 900, inferior sagittal sinus 902, sigmoid sinus 904, transverse sinus 906, or straight sinus 908.

[0176] In other embodiments, the first intravascular carrier 108A carrying the first electrode array 102A may be implanted in the superficial cerebral vein of the subject. For example, the first intravascular carrier 108A carrying the first electrode array 102A may be implanted in at least one of the following veins: Rabe vein 910, Trollado vein 912, Sylvian vein 914, and Roland vein 916.

[0177] Furthermore, the first intravascular carrier 108A carrying the first electrode array 102A can be implanted in the deep cerebral vein of the subject. For example, the first intravascular carrier 108A carrying the first electrode array 102A can be implanted in at least one of the following: Rosenthal vein 918, Galen vein 920, superior thalamostratable vein 922, inferior thalamostratable vein 924, and internal cerebral vein 926.

[0178] In a further embodiment, the first intravascular carrier 108A carrying the first electrode array 102A may also be implanted in at least one of the central sulcus vein, the posterior central sulcus vein, and the anterior central sulcus vein. In an additional embodiment, the first intravascular carrier 108A may be implanted or configured to be implanted in a vessel extending through the hippocampus or amygdala of a subject.

[0179] Once implanted, the first electrode array 102A may be configured to detect or record electrophysiological signals of a subject that are associated with or correlated with the onset of epileptic seizures. In some embodiments, the electrophysiological signals may be local potentials (LFPs) and / or intracranial / cortical EEGs measured within the cerebral or cortical blood vessels (e.g., venous sinuses or cortical veins). In other embodiments, the electrophysiological signals may be cortical electroencephalogram (ECoG) signals.

[0180] As described above, the neural modulation unit 104 may further include a telemetry unit 120 or a telemetry module (e.g., a telemetry hardware module, a telemetry software module, or a combination thereof). The telemetry unit 120 may be configured to analyze electrophysiological signals detected or recorded by the first electrode array 102A. For example, one or more processors in the neural modulation unit 104 (or the telemetry unit 120 within the neural modulation unit 104) can be programmed to execute instructions stored in one or more memory units to analyze electrophysiological signals by (i) comparing detected signals against one or more thresholds (e.g., detecting signal spikes), (ii) detecting specific signal patterns or rhythmic activity in a specific frequency range, (iii) comparing absolute inter-sample amplitude differences within a predetermined time window, (iv) measuring changes in signal energy, or a combination thereof. Next, the nerve modulator 104 can instruct the pulse generator 110 (for example, a pulse generator provided as part of the nerve modulator 104, or a pulse generator separate from the nerve modulator 104) to generate electrical impulses that stimulate a target site in the body or a target site for stimulation via a second electrode array 102B coupled to a second intravascular carrier 108B.

[0181] As described above, when the target site in the body is the subject's vagus nerve, the second intravascular carrier 108B can be implanted in the internal jugular vein (either the right or left internal jugular vein) or the internal carotid artery.

[0182] In other embodiments, the target site in the body or the target site for stimulation may be the subject's cerebellum 928. In these embodiments, the second intravascular carrier 108B carrying the second electrode array 102B may be implanted in at least one of the subject's sigmoid sinus 904 and straight sinus 908. Furthermore, the second intravascular carrier 108B carrying the second electrode array 102B may also be implanted in the subject's transverse sinus 906. At least a portion of the cerebellum 928 is adjacent to (i.e., separated by less than 2.0 mm from) the sigmoid sinus 904, straight sinus 908, and transverse sinus 906.

[0183] In additional embodiments, the target site in the body or the target site for stimulation may be the subject's motor cortex 930. In further embodiments, the second intravascular carrier 108B carrying the second electrode array 102B may be implanted in at least one of the patient's inferior sagittal sinus 902, central sulcus vein, posterior central sulcus vein, and anterior central sulcus vein. Furthermore, the second intravascular carrier 108B carrying the second electrode array 102B may also be implanted in the subject's superior sagittal sinus 900. At least a portion of the motor cortex 930 is adjacent to (i.e., separated by less than 2.0 mm from) the superior sagittal sinus 900, central sulcus vein, posterior central sulcus vein, and anterior central sulcus vein.

[0184] Furthermore, at least a portion of the motor cortex 930 is located approximately 5.0 mm to 10.0 mm from the inferior sagittal sinus 902. When the second intravascular carrier 108B carrying the second electrode array 102B is implanted in the inferior sagittal sinus 902, the target site in the body to be stimulated may also include the subject's fornix 944. The fornix 944 may be located approximately 10.0 mm to 15.0 mm from the inferior sagittal sinus 902.

[0185] In a further embodiment, the second intravascular carrier 108B carrying the second electrode array 102B may be implanted in a superficial cerebral vein. For example, the second intravascular carrier 108B carrying the second electrode array 102B may be implanted in at least one of the following veins: Rabe vein 910, Trollado vein 912, Sylvian vein 914, and Roland vein 916.

[0186] In some embodiments, the second intravascular carrier 108B carrying the second electrode array 102B can be implanted in a deep cerebral vein. For example, the second intravascular carrier 108B carrying the second electrode array 102B can be implanted in at least one of the Rosenthal vein 918, the Galen vein 920, the superior thalamostratable vein 922, and the internal cerebral vein 926.

[0187] When the second intravascular carrier 108B, which carries the second electrode array 102B, is implanted in the Rosenthal vein 918, the target site in the body to be stimulated may include at least one of the cerebellum 928, anterior nucleus thalamus 932, central nucleus thalamus 934, hippocampus 936, subthalamic nucleus 938, and posterior zone of uncertainty 940. The Rosenthal vein 918 may be located in a range of about 10.0 mm to about 15.0 mm from at least a portion of the cerebellum 928, anterior nucleus thalamus 932, and central nucleus thalamus 934. The Rosenthal vein 918 may be located in a range of about 5.0 mm to about 10.0 mm from at least a portion of the hippocampus 936, subthalamic nucleus 938, and posterior zone of uncertainty 940.

[0188] When the second intravascular carrier 108B, which carries the second electrode array 102B, is implanted in the internal cerebral vein 926, the target site in the body to be stimulated may include at least one of the anterior thalamus 932, central nucleus of the thalamus 934, hypothalamus 942, fornix 944, and posterior zone of uncertainty 940. The internal cerebral vein 926 may be approximately 10.0 mm to approximately 15.0 mm from at least a portion of the hypothalamus 942 and posterior zone of uncertainty 940. The internal cerebral vein 926 may be approximately 5.0 mm to approximately 10.0 mm from at least a portion of the anterior thalamus 932. The internal cerebral vein 926 may be approximately 2.0 mm to approximately 5.0 mm from at least a portion of the fornix 944. The internal cerebral vein 926 may be adjacent to the central nucleus of the thalamus 934 (i.e., separated by less than 2.0 mm).

[0189] When the second intravascular carrier 108B, which carries the second electrode array 102B, is implanted in the superior thalamostratable vein 922, the target site in the body to be stimulated may include at least one of the anterior nucleus thalamus 932, the central nucleus thalamus 934, and the fornix 944. The superior thalamostratable vein 922 may be adjacent to (i.e., separated by less than 2.0 mm) the anterior nucleus thalamus 932, the central nucleus thalamus 934, and the fornix 944.

[0190] In certain embodiments, the second intravascular carrier 108B carrying the second electrode array 102B may be further implanted or configured to be implanted in a blood vessel extending through the hippocampus or amygdala of a subject.

[0191] In some embodiments, stimulating a target site in the body or a target site of stimulation via a second electrode array 102B can increase blood flow to the target site in the body or increase levels of specific neurotransmitters involved in suppressing seizure activity. Furthermore, stimulating a target site in the body via a second electrode array 102B can also result in sodium channel inactivation (using high-frequency stimulation), prolonged inhibition of specific neurotransmitters (using high-frequency stimulation), and / or glutamatergic inhibition (using both low-frequency and high-frequency stimulation).

[0192] For example, when stimulating a target area of ​​the cortex or cerebrum, a bipolar type can be used, in which the voltage of the electrical impulse is increased from 1V to 7V in 0.25V increments. The generated electrical impulse can have a pulse width of 90μS to approximately 540μS, a frequency of approximately 3Hz to 5Hz in the low-frequency range, and approximately 50Hz to 130Hz in the high-frequency range.

[0193] While recording and stimulation using electrode arrays 102 coupled to different intravascular carriers 108 have been discussed, this disclosure intends for the same intravascular carrier (see, for example, intravascular carrier 214 shown in Figure 2D) to be able to carry both a first electrode array 102A and a second electrode array 102B. For example, expandable stents and scaffolds can carry both recording electrode arrays and stimulating electrode arrays.

[0194] Figure 10 illustrates a method according to one embodiment for deploying or delivering intravascular carriers 108 (e.g., a first intravascular carrier 108A and a second intravascular carrier 108B) to their respective implantation sites. Although two intravascular carriers 108 are deployed in the figure, it is intended by this disclosure that a single intravascular carrier (see, for example, intravascular carrier 214 in Figure 2D) or three or more intravascular carriers carrying a separate electrode array 102 can also be delivered using a similar apparatus or method.

[0195] As shown in Figure 10, the first delivery catheter 1000 can be deployed into the superior sagittal sinus 900 through a jugular venotomy. The first delivery catheter 1000 can be deployed under angiography guidance. Although the superior sagittal sinus 900 is shown in the drawing, those skilled in the art will understand that the catheter and carrier can be deployed into any vein, sinus, or artery of the subject.

[0196] A first intravascular carrier 108A (not shown in Figure 10, see Figure 1) carrying the first electrode array 102A can be deployed through a first delivery catheter 1000 or delivered by other means. For example, the first intravascular carrier 108A may be a stent-electrode array 109 configured to self-expand to a predetermined position within the superior sagittal sinus 900.

[0197] In some embodiments, the first electrode array 102A coupled to the first intravascular carrier 108A can be used as a recording electrode array. In other embodiments, the first electrode array 102A can be used as a stimulating electrode array, or as both a recording electrode array and a stimulating electrode array. Once the first intravascular carrier 108A is positioned, the first delivery catheter 1000 can be removed from the subject's vascular system.

[0198] Figure 10 also illustrates that a second delivery catheter 1002 can be deployed through the same jugular vein incision to the internal cerebral vein 926 above the anterior nucleus thalamus 932. The second delivery catheter 1002 can be deployed under angiography guidance.

[0199] A second intravascular carrier 108B (not shown in Figure 10, see Figure 1) carrying the second electrode array 102B can be deployed through a second delivery catheter 1002 or delivered by other means. For example, the second intravascular carrier 108B may be a stent-electrode array 109 configured to self-expand to a predetermined position within the internal cerebral vein 926.

[0200] In some embodiments, the second electrode array 102B coupled to the second intravascular carrier 108B can be used as a stimulating electrode array. In other embodiments, the second electrode array 102B can be used as a recording electrode array, or as both a stimulating electrode array and a recording electrode array. Once the second intravascular carrier 108B is positioned, the second delivery catheter 1002 can be removed from the subject's vascular system.

[0201] Furthermore, as shown in Figure 10, a first transmission lead 106A coupled to a first electrode array 102A on a first intravascular carrier 108A extends through the subject's neck (e.g., through the jugular vein), and the proximal end of the first transmission lead 106A can be inserted into a neuromodulatory unit 104 implanted in the subject's body (e.g., into a header unit 114, see Figure 1). In addition, a second transmission lead 106B coupled to a second electrode array 102B on a second intravascular carrier 108B extends through the subject's neck, and the proximal end of the second transmission lead 106B can be inserted into the neuromodulatory unit 104.

[0202] Figure 11 illustrates another example of a method for deploying or delivering intravascular carriers 108 (e.g., a first intravascular carrier 108A and a second intravascular carrier 108B) to their respective implantation sites. Although two intravascular carriers 108 are deployed in the figure, it is intended by this disclosure that a single intravascular carrier (e.g., see intravascular carrier 214 in Figure 2D) or three or more intravascular carriers carrying a separate electrode array 102 can also be delivered using similar apparatus or methods.

[0203] As shown in Figure 11, the first delivery catheter 1100 can be deployed into the superior sagittal sinus 900 through a jugular venotomy. The first delivery catheter 1100 can be deployed under angiography guidance. Although the superior sagittal sinus 900 is shown in the figure, those skilled in the art will understand that the catheter and carrier can be deployed into any vein, sinus, or artery of the subject.

[0204] A first intravascular carrier 108A (not shown in Figure 11, see Figure 1) carrying the first electrode array 102A can be deployed through a first delivery catheter 1100 or delivered by other means. For example, the first intravascular carrier 108A may be a stent-electrode array 109 configured to self-expand to a predetermined position within the superior sagittal sinus 900.

[0205] In some embodiments, the first electrode array 102A coupled to the first intravascular carrier 108A can be used as a recording electrode array. In other embodiments, the first electrode array 102A can be used as a stimulating electrode array, or as both a recording electrode array and a stimulating electrode array. Once the first intravascular carrier 108A is positioned, the first delivery catheter 1000 can be removed from the subject's vascular system.

[0206] Figure 11 also illustrates that the first delivery catheter 1100 can be retracted proximal, and the second delivery catheter 1102 can be deployed through the retracted first delivery catheter 1100. The second delivery catheter 1002 can be deployed into the internal cerebral vein 926 above the anterior nucleus thalamus 932. The second delivery catheter 1002 can be deployed under angiography guidance.

[0207] A second intravascular carrier 108B (not shown in Figure 11, see Figure 1) carrying the second electrode array 102B can be deployed through a second delivery catheter 1002 or delivered by other means. For example, the second intravascular carrier 108B may be a stent-electrode array 109 configured to self-expand to a predetermined position within the internal cerebral vein 926.

[0208] In some embodiments, the second electrode array 102B coupled to the second intravascular carrier 108B can be used as a stimulating electrode array. In other embodiments, the second electrode array 102B can be used as a recording electrode array, or as both a stimulating electrode array and a recording electrode array. Once the second intravascular carrier 108B is positioned, the second delivery catheter 1102 can be removed from the subject's vascular system.

[0209] A first transmission lead 106A, coupled to a first electrode array 102A on a first intravascular carrier 108A, extends through the subject's neck (e.g., through the jugular vein), and the proximal end of the first transmission lead 106A can be inserted into a neuromodulatory unit 104 implanted in the subject's body (e.g., into a header unit 114, see Figure 1). In addition, a second transmission lead 106B, coupled to a second electrode array 102B on a second intravascular carrier 108B, extends through the subject's neck, and the proximal end of the second transmission lead 106B can be inserted into the neuromodulatory unit 104.

[0210] Figure 12 illustrates another example of a method for deploying or delivering intravascular carriers 108 (e.g., a first intravascular carrier 108A and a second intravascular carrier 108B) to their respective implantation sites. Although two intravascular carriers 108 are deployed in the figure, it is intended by this disclosure that three or more intravascular carriers can also be delivered using similar apparatus or methods.

[0211] As shown in Figure 12, the delivery catheter 1200 can be deployed through a jugular venotomy to the superior sagittal sinus 900 and then continued to the internal cerebral vein 926 above the anterior nucleus thalamus 932. The delivery catheter 1200 can be deployed under angiography guidance.

[0212] Although the drawing shows the superior sagittal sinus 900, those skilled in the art will understand that the catheter and carrier can be deployed into any vein, sinus, or artery of the subject.

[0213] A second intravascular carrier 108B (not shown in Figure 12, see Figure 1) carrying the second electrode array 102B can be deployed through a delivery catheter 1200 or delivered by other means. For example, the second intravascular carrier 108B may be a stent-electrode array 109 configured to self-expand to a predetermined position within the internal cerebral vein 926.

[0214] In some embodiments, the second electrode array 102B coupled to the second intravascular carrier 108B can be used as a recording electrode array. In other embodiments, the second electrode array 102B can be used as a stimulating electrode array, or as both a recording electrode array and a stimulating electrode array. Once the second intravascular carrier 108B is positioned, the delivery catheter 1200 can be retracted until its distal end is positioned to deploy the first intravascular carrier 108A into the superior sagittal sinus 900 of the subject. The first intravascular carrier 108A can carry the first electrode array 102A (not shown in Figure 12, see Figure 1). The first intravascular carrier 108A may be a stent-electrode array 109 configured to self-expand into a predetermined position within the superior sagittal sinus 900.

[0215] In some embodiments, the first electrode array 102A coupled to the first intravascular carrier 108A can be used as a stimulating electrode array. In other embodiments, the first electrode array 102A can be used as a recording electrode array, or as both a stimulating electrode array and a recording electrode array. Once the first intravascular carrier 108A is positioned, the delivery catheter 1200 can be removed from the subject's vascular system.

[0216] When the delivery catheter 1200 is retracted, a single transmission lead 106 connecting the first intravascular carrier 108A and the second intravascular carrier 108B can be exposed. The single transmission lead 106 extends through the subject's neck (e.g., through the jugular vein), and the proximal end of the transmission lead 106 can be inserted into a nerve modulatory unit 104 implanted in the subject's body (e.g., into a header unit 114, see Figure 1).

[0217] Figure 13 illustrates a delivery catheter 1300 according to one embodiment, comprising a first intravascular carrier 108A and a second intravascular carrier 108B connected by a branched transmission lead 1302. As shown in Figure 13, the first branch 1304 of the branched transmission lead 1302 can be connected to or coupled to the first intravascular carrier 108A, and the second branch 1306 of the branched transmission lead 1302 can be connected to or coupled to the second intravascular carrier 108B. At least one guidewire 1308 can extend alongside at least one of the branches of the branched transmission lead 1302. The guidewire 1308 can extend through the lumen of one of the intravascular carriers 108 (e.g., the second intravascular carrier 108B) and be detachably coupled to the tip 1310 of the intravascular carrier 108.

[0218] Another method for deploying or delivering the intravascular carriers 108 (e.g., a first intravascular carrier 108A and a second intravascular carrier 108B) to their respective implantation sites may include deploying a delivery catheter 1300 into the superior sagittal sinus 900 through a jugular vein incision. The delivery catheter 1300 may be deployed under angiography guidance.

[0219] The first intravascular carrier 108A (not shown in Figure 13, see Figure 1), which carries the first electrode array 102A, can be deployed through a delivery catheter 1300 or delivered by other means. For example, the first intravascular carrier 108A may be a stent-electrode array 109 configured to self-expand to a predetermined position within the superior sagittal sinus 900.

[0220] In some embodiments, the first electrode array 102A coupled to the first intravascular carrier 108A can be used as a recording electrode array. In other embodiments, the first electrode array 102A can be used as a stimulating electrode array, or as both a recording electrode array and a stimulating electrode array. Once the first intravascular carrier 108A is positioned, the delivery catheter 1300 can be retracted proximally, and the second intravascular carrier 108B (not shown in Figure 13, see Figure 1), which carries the second electrode array 102B, can be deployed through the retracted delivery catheter 1300 to a second implantation site (e.g., the internal cerebral vein 926 above the anterior nucleus thalamus 932 of the subject). A guidewire 1308 can be used to guide the second intravascular carrier 108 to a predetermined position within the second implantation site.

[0221] For example, the second intravascular carrier 108B may be a stent-electrode array 109 configured to self-expand to a predetermined position within a deployed vessel, such as the internal cerebral vein 926. In some embodiments, the second electrode array 102B coupled to the second intravascular carrier 108B may be used as a stimulating electrode array. In other embodiments, the second electrode array 102B may be used as a recording electrode array, or as both a stimulating electrode array and a recording electrode array. Once the second intravascular carrier 108B is in place, the delivery catheter 1300 and guidewire 1308 can be removed from the subject's vascular system.

[0222] By retracting the delivery catheter 1300, a branched transmission lead 1302 connecting the first intravascular carrier 108A and the second intravascular carrier 108B can be exposed. The transmission lead 1302 extends through the subject's neck (e.g., through the jugular vein), and the proximal end of the transmission lead 1302 can be inserted into a nerve modulatory unit 104 implanted in the subject's body (e.g., into a header unit 114, see Figure 1).

[0223] One technical advantage of the closed-loop neural modulation system 100 disclosed herein is that the system 100 can be delivered to a blood vessel near the site of interest in the body / to be stimulated via angiography with minimal invasiveness, without physically contacting the site of interest in the body / to be stimulated (e.g., the vagus nerve) or damaging the site of interest in the body / to be stimulated (e.g., damaging the vagus nerve).

[0224] Another technical advantage of the neuromodulatory system 100 disclosed herein is that when a first intravascular carrier 108A (carrying a first electrode array 102A or a recording electrode array) is implanted in a cortical / cerebral vein or sinus, and a second intravascular carrier 108B (carrying a second electrode array 102B or a stimulating electrode array) is implanted in a cortical / cerebral vein or sinus or in a vein or artery superior to the subject's skull, the subject's skull can function as a protective enclosure to protect the carriers from potentially destructive external forces and enhance the electrophysiological signals being detected or recorded.

[0225] A further technical advantage of the neuromodulatory system 100 disclosed herein is that the system 100 can provide closed-loop or responsive stimulation, in which electrophysiological signals from a subject are detected or otherwise acquired and used as the driving force to trigger electrical stimulation. A further advantage of a system operating in closed-loop or responsive mode is that the battery life of the electronic components can be extended by activating the various electronic components of the system only when a seizure is imminent or when the subject is observed to be in a state of high seizure risk.

[0226] Several embodiments have been described. Nevertheless, those skilled in the art will understand that various changes and modifications can be made to this disclosure without departing from the spirit and scope of the embodiments. Elements of systems, devices, apparatus, and methods shown with any embodiment are illustrative for a particular embodiment and can be used in combination with other embodiments in this disclosure or otherwise. For example, the steps of any method depicted in the figures or described in this disclosure do not require a specific shown or described sequence to achieve the desired result. In addition, other step operations may be provided to obtain the desired result, or steps or operations may be removed or omitted from the described method or process. Furthermore, any component or part of any apparatus or system described or depicted in the figures may be removed, deleted or omitted to achieve the desired result. Also, certain components or parts of systems, devices, or apparatuses shown or described herein have been omitted for brevity and clarity.

[0227] Therefore, other embodiments may fall within the scope of the following claims, and the specification and / or drawings may be considered illustrative rather than restrictive.

[0228] Each of the individual modifications or embodiments described and illustrated herein has individual components and elements that can be easily separated or combined with elements of any other modifications or embodiments. Multiple modifications can be made to adapt a particular situation, material, composition of substance, process, one or more actions of a process, or one or more steps of the present invention to the object, spirit, or scope of the invention.

[0229] The methods described herein can be used to perform the described events in any logically possible order, or in the order described. Furthermore, additional steps or operations may be added or removed to achieve the desired results.

[0230] Furthermore, if a range of values ​​is defined, all values ​​interposing between the upper and lower limits of that range, and any other defined or interposing values ​​within that defined range, shall be included within the scope of the present invention. In addition, any element of an aspect of the present invention may be defined and claimed independently or in combination with any one or more elements described herein. For example, a description of a range of 1 to 5 should be considered as disclosing subranges such as 1 to 3, 1 to 4, 2 to 4, 2 to 5, 3 to 5, and individual numerical values ​​within those ranges, such as 1.5, 2.5, etc., and increments of all or part of these.

[0231] All existing subject matter referenced herein (e.g., publications, patents, patent applications) is incorporated herein by whole-word unless such subject matter may conflict with the subject matter of the present invention (in which case the information present herein shall prevail). The referenced items are provided solely for disclosure prior to the filing date of this application. Nothing in this specification shall be construed as admitting that the present invention has no prior rights to such material by prior invention.

[0232] References to singular items imply the possibility of multiple identical items existing. More specifically, as used herein and in the appended claims, singular “a,” “an,” “said,” and “the” imply multiple references unless the context clearly indicates otherwise. Furthermore, it should be noted that the claims may be constructed to exclude any element. This statement is therefore intended to serve as prior art for using exclusive terms such as “alone” and “only,” or for using “negative” limitations, in relation to the description of elements of the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the invention pertains.

[0233] The phrase "at least one" means any combination of one or more items or components when modifying multiple items or components (or an enumerated list of items or components). For example, the phrase "at least one of A, B, and C" means (i) A; (ii) B; (iii) C; (iv) A, B, and C; (v) A and B; (vi) B and C; or (vii) A and C.

[0234] For understanding the scope of this disclosure, the terms “including” and their derivatives as used herein are intended to be open terms that identify the presence of described features, elements, components, groups, integers, and / or steps, but do not exclude the presence of other undescribed features, elements, components, groups, integers, and / or steps. The same applies to similar phrases such as “including,” “having,” and their derivatives. The terms “part,” “section,” “part,” “component,” “element,” and “component” as used in the singular may mean either one part or more parts. Directional terms as used herein, such as “forward, backward, upward, downward, vertical, horizontal, downward, transverse, and longitudinal,” and any other similar directional terms, mean that the position of the device or equipment, or the direction of the device or equipment, is translated or moved.

[0235] Finally, as used herein, terms of degree such as “substantially,” “about,” and “approximately” mean a specified value, or a reasonable deviation from a specified value and a specified value (e.g., a deviation of up to ±0.1%, ±1%, ±5%, or ±10%, such that the final result does not change substantially or substantially). For example, “about 1.0 cm” can be interpreted as “1.0 cm” or “0.9 cm to 1.1 cm.” When using terms of degree such as “about” or “approximately” for numbers or values ​​that are part of a range, these terms can be used to add or subtract the minimum and maximum numbers or values.

[0236] This disclosure is not intended to be limited to any specific form defined herein, but rather to cover substitutes, modifications, and equivalents of the variations or embodiments described herein. Furthermore, the scope of this disclosure fully encompasses other variations or embodiments that may be obvious to those skilled in the art in view of this disclosure.

Claims

1. A system for detecting, measuring, recording, stimulating, and regulating brain activity, A carrier comprising multiple electrodes and one or more base material members, wherein a conductive material is embedded in the one or more base material members, A remote measurement unit is electrically connected to the carrier via a transmission lead, A flexible, hollow delivery device configured to move the carrier from an access site within a blood vessel to a target site outside the blood vessel within the skull of a subject, Equipped with, The conductive material and the transmission lead are configured to transmit the electrical signal recorded at the target site to the remote measurement unit. A system in which the electrodes of the carrier are configured to be electrically in communication with the nerve tissue of the subject's brain at the target site.

2. The system according to claim 1, wherein the telemetry unit and the carrier are further configured to enable one or more activities, including detection of cortical activity, stimulation of neurons, and regulation of neural activity.

3. The system according to claim 1, wherein the conductive material includes a wire extending over the length of the carrier.

4. The system according to claim 3, wherein the wire is connected to the remote measurement unit by a header unit.

5. The system according to claim 1, wherein the flexible, hollow delivery device is a catheter configured to house the carrier and deliver it to the access site, and the catheter is configured to retract in a proximal direction.

6. The system according to claim 5, wherein the catheter is configured to be detachable from the carrier and is removable from the subject after the carrier has been deployed, thereby allowing the carrier to maintain electrical communication with the nerve tissue of the subject's brain.

7. The system according to claim 1, wherein the carrier is confined to a small volume so as to be housed within the flexible, hollow delivery device while being moved through the access site to the target site outside the blood vessel.

8. The system according to claim 1, wherein the flexible, hollow delivery device is further configured to move the carrier out of the blood vessel and to the target site within the skull of the subject through a puncture site at the access site.

9. The system according to claim 1, wherein the remote measurement unit is implantable and configured to wirelessly transmit recorded nerve signals to an external receiver.

10. The system according to claim 1, wherein the remote measurement unit is configured to receive power wirelessly via inductive coupling.

11. The system according to claim 1, wherein the transmission lead includes a plurality of insulating conductors and a connector region having a plurality of contact elements electrically coupled to the insulating conductors.

12. The system according to claim 1, wherein the conductive material includes a plurality of conductive paths embedded in one or more base material members and extending longitudinally along the carrier.

13. The system according to claim 1, wherein the plurality of electrodes are arranged along the carrier in at least one of a circumferential pattern and a longitudinal pattern.

14. The system according to claim 1, wherein the carrier self-expands from a delivery form to a deployment form at the target site.

15. The system according to claim 1, wherein the flexible, hollow delivery device includes one or more radiopaque markers configured to indicate a deployment position.

16. A method for detecting, measuring, recording, stimulating, and regulating brain activity, A step of moving a carrier within the skull of a subject from an access site within a blood vessel to a target site outside the blood vessel, using a flexible, hollow delivery device, wherein the carrier comprises a plurality of electrodes and one or more base members, the one or more base members of which are embedded with a conductive material, The steps include transmitting the electrical signal recorded at the target location to the remote measurement unit via the conductive material and transmission lead, Includes, The remote measurement unit is electrically connected to the carrier via the transmission lead. A method wherein the electrodes of the carrier are configured to communicate electrically with the nerve tissue of the subject's brain at the target site.

17. The method according to claim 16, further comprising the step of moving the carrier out of the blood vessel and into the target site within the skull of the subject, through a puncture site at the access site, using the flexible, hollow delivery device.

18. The method according to claim 16, further comprising the step of wirelessly transmitting nerve signals recorded from the remote measurement unit to an external receiver.

19. The method according to claim 16, further comprising the step of wirelessly supplying power to the remote measuring unit via inductive coupling.

20. The method according to claim 16, further comprising the step of causing the carrier to self-expand from a delivery form to a deployment form at the target site.

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