Sinus implant for deep brain stimulation and sensing

Abstract

An implant that can be implanted non-invasive or minimally-invasively into the sphenoid cavity of a subject for delivery of stimulation to deep brain reward circuit nodes of the brain and / or to drive hormonal release through stimulation of nuclei in the hippocampus or cells in the pituitary or nearby structures such as blood vessels. The implant is alternatively or additionally capable of sensing signals in the deep brain, and for powering deep-brain implants (i.e., devices placed in the brain that are difficult to power from the scalp due to distance).

Description

Attorney Docket: 8350.2024-278WOSinus Implant for Deep Brain Stimulation and SensingRelated Applications

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 700,109, filed September 1 , 2024, the contents of which are incorporated herein in their entirety.Background

[0002] Non-invasive / minimally-invasive deep-brain stimulation is of great interest. The brain's "reward circuit" consists of multiple cortical and subcortical (deep-brain) nodes, as shown in FIG. 1 which include the orbitofrontal cortex (OFC), hippocampus, amygdala, nucleus accumbens, thalamus, Broadmann Area 25, etc. These areas of the brain processes reward and punishment, and are implicated in several conditions, for example, depression, suicidal ideation, post-traumatic stress disorder (PTSD), epilepsy and substance use disorders.

[0003] Such conditions may be successfully treated using implanted electrodes in nodes of the reward circuitry to electrically stimulate these brain areas. For example, deep-brain stimulation (DBS) has been used to stimulate Brodmann Area 25 (subgenual cingulate area) for patients with treatment-resistant depression. In another example, the lateral OFC was stimulated and acute improvement in mood-state was observed in patients with moderate-to-severe depression. DBS treatments are also used experimentally forAttorney Docket: 8350.2024-278WO patients with brain injuries and those in vegetative / minimally-conscious state, with good success rates, and some of these targets are outside of the standard reward circuit but still lie in the deep brain.

[0004] However, DBS requires a sophisticated surgical procedure to implant the components of the system, which include electrodes, a battery, and the associated circuitry. This process carries risk of intracranial hemorrhage and infection. Moreover, the stimulation target region cannot be changed once the electrodes are implanted inside the brain. Non-invasive techniques such as transcranial magnetic stimulation (TMS), transcranial focused ultrasound stimulation (tFUS), and transcranial electrical stimulation (TES) have lower risk and are steerable, but are also limited in their depth, resolution, and effect. TMS and TES effects are relatively shallow (i.e ., 2 to 4 cm below the cortical surface), and are unable to target deep brain structures, especially near the ventral side of the brain. TES passes electrical currents to directly stimulate neurons resulting, for example, in motor evoked potentials when targeting the motor cortex. However, these non-invasive techniques traditionally inject energy from the top of the head (i.e., through the scalp), and therefore require higher amplitudes to affect neurons at large depths. This leads to stimulation of undesired shallow targets (which lowers focality), which can cause unintended side effects and intolerable scalp pain or even tissue damage.Attorney Docket: 8350.2024-278WOSummary of the Invention

[0005] The device disclosed herein can be implanted into the sphenoid, a cavity in the head located under the skull base, via a non-surgical procedure or a minimally invasive surgical procedure. This allows stimulation of areas of the brain using the entirely new concept of transnasal stimulation through the skull base, potentially driving reward circuit nodes (such as subgenual / subcallosal cingulate, amygdala, nucleus accumbens, hippocampus which, invasively, have been shown to be stimulation targets for treatment of depression, PTSD, TBI etc.), as well as driving hormonal release through stimulation of nuclei in the hippocampus or cells in the pituitary. The device is also capable of sensing signals in the deep brain (e.g. using optical and / or electrical recordings) and could also power deep-brain implants (i.e., devices placed in the brain that are difficult to power from the scalp due to distance).Brief Description of the Drawings

[0006] FIG. 1 is an illustration showing important nodes in the reward circuitry of the brain.

[0007] FIG. 2 is a schematic view of the implant.

[0008] FIG. 3 is a schematic view of a brain showing placement of the implant.

[0009] FIG. 4 is a photograph of a prototype of the implant.

[0010] FIG. 5A is a schematic diagram depicting a study conducted in a cadaver to determine the effectiveness of the implant. FIG. 5B is a photograph of the device implanted in the cadaver.Attorney Docket: 8350.2024-278WODetailed Description

[0011] The implant is shown schematically in FIG. 2. A plurality of spokes 202 containing transducers 201 emanate from a central portion. Transducers 201 convert energy from the device into the brain and vice versa. For example, transducers 201 can be electrodes, coils, ultrasonic, optical, chemical, thermal, etc. Transducers 201 may be unidirectional or bidirectional and be used for stimulation and / or sensing. In the case of electrical stimulation or measurement, at least 2 transducers (i.e., electrodes) 201 are needed. More transducers 201 may help with variability in placement because sinuses vary across individuals. Increased numbers of transducers 201 may also help with spatial targeting of stimulation or sensing. It is not necessary that all of the electrodes be used during the delivery of electrical stimulation. Similar designs could be used for generating magnetic fields where, instead of individual spokes 202, the elements that emanate from the central portion comprise coils.

[0012] Part of the central portion comprises circuitry 204 for delivering energy to the transducers 201 placed on the distal ends of the spokes (stimulation currents to electrodes, power to ultrasound transducers or light to waveguides). The circuitry may include a wired or wireless communications interface to allow communication with an interface outside of the body of the subject wherein various parameters of the stimulation (i.e., shape of wave, frequency, amplitude, etc.) are designed. The parameters of the stimulation may be determined, for example, by software, which may include a machine learning component, executing on a processor. Alternatively, all circuitry required to form the stimulation signals may be present on circuitry 204.Attorney Docket: 8350.2024-278WOCircuitry 204 may have components allowing programming of instructions required to generate the appropriate signals prior to insertion of the implant.

[0013] The central portion 204 houses also includes the means of powering the unit. The means of power in can be, for example, a battery or elements for wireless power transfer / harvesting, such as a coil or ultrasound transducers.

[0014] In one embodiment, spokes 202 may include a fluidic channel that can be filled or emptied with a liquid or air to change the stiffness of spokes 202. The channels can be emptied or depressurized during insertion and filled or pressurized after insertion to provide positive contact of the transducers 201 with the tissue of the sphenoid cavity. In other embodiments, inflatable balloons can be used to push the electrodes close to or in contact with the sphenoid walls.

[0015] In yet other embodiments, wire-meshes that expand similar to how stents operate may be used. Similar implants can be placed in the frontal sinus or the ethmoid sinus for proximity to frontal and medial anterior regions of the brain.

[0016] In some embodiments, the spokes 202 can extent outside of the sinus where the device is implanted such as to enable the spokes to reach other parts of the nasal cavities, such as under the cribriform plate, to access more frontal regions of the brain.

[0017] In another embodiment, spokes 202 are collapsed in a strained configuration and encapsulated in a dissolvable capsule. Upon tissue contact, the capsule dissolves, and releases spokes 202, which unfold due to the applied strain, and make contact with the tissue.Attorney Docket: 8350.2024-278WO

[0018] Depending on the intended use, spokes 202 may be composed of flexible materials, for example, polymers such as polyimide, parylene or PDMS), or rigid materials, for example, polymers such as acrylic, or metal such as steel, titanium or platinum. In the case of wherein spokes 202 are i nf lata b le / fi Ila b le, the spokes would likely be composed of a flexible or stretchable polymer, for example, PDMS, which may be used in combination with other polymers like parylene. In most applications, there would be a signal connection from the central circuit 204 to the transducer 201 on the spokes, which could be electrical (requiring wiring made of metal or conductive polymers), optical (requiring waveguides mode out of optical ceramics or polymers), or chemical (implemented using microfluidic channels). The transducer 201 would then have different materials depending on the interface modality. For example, for electrical modalities, metal electrodes would be used, such as gold, platinum, titanium. For ultrasonic modalities, a piezoelectric material, such as PZT or PVDF would be used. For magnetic field modalities, coils made of high conductivity metal like copper or gold / silver would be used.

[0019] The central portion may be implemented as a flexible printed circuit board (PCB) (polyimide substrate with copper wiring) that could be microfabricated out of either flexible substrates (e.g., polyimide, parylene, PDMS) or rigid substrates (e.g., FR4, other plastic or metal substrates). The power source may have other materials as well, depending on the implementation (batteries have exotic material mixtures like Lilon , AgOx; other energy harvesting methods may use other materials).Attorney Docket: 8350.2024-278WO

[0020] FIG. 3 shows the implant in situ in the sphenoid cavity of a subject. The implant is intended to be positioned using minimally invasive techniques through the nostrils and sinus passages of the subject.

[0021] FIG. 4 shows a prototype that delivers electric currents through electrodes. A flexible PCB 402 has two wing-like flexible PCB electrodes 404 tipped by transducers 406. The circuit board 402 houses the stimulation circuitry. Having flexible PCB material or similar flexible substrates enables improved contact with the walls of the sphenoid sinus through capillary action. The circuitry also includes a clock and an ultra-low power pulse generator, which takes a low-voltage DC input (e.g., from a battery) to generate a high-voltage output pulse.

[0022] The device is also capable of sensing electrical signals from the brain, independently of or simultaneously with the delivery of the electrical stimulation. The device is also capable of being used to inject or sense ultrasound, light, or heat into tissue for diverse effects. In various embodiments, a first subset of the transducers may be used for delivering therapy, while a second subset of the transducers may be used for simultaneous measurement. A sensing embodiment could be used independently to localize epileptic sources for temporal lobe epilepsy, or sense activity in the reward ci rcuit / li mbic system / circuit of Papez. Using, for example, optical / ultrasound sensing, it can also sense hemodynamic and / or blood flow activity in nearby blood vessels (e.g., those in / near the pituitary, in the cavernous sinus, and around the branch of the internal carotid artery that is close to the sphenoid sinus).Attorney Docket: 8350.2024-278WO

[0023] The main issue in non-invasive / minimally-invasive deep-brain stimulation is that it is difficult to drive currents deep in the brain. U.S. Patent. App. No. 18 / 742,524, filed June 13, 2024, discloses a system and method that utilizes electrodes inserted transnasally, along with scalp electrodes, to deliver currents deep in the brain. The implant disclosed herein may be used as part of that system. This disclosure proposes a minimally invasive wireless implant that can be implanted in the sphenoid sinus for chronic stimulation and / or sensing lasting days, weeks, or even months. Sensing capabilities enable the stimulation to be delivered in a closed loop modality by monitoring activity in the deep-brain to track changes due to stimulation. Disclosed therein is a technique for the non-invasive stimulation of deep brain regions, including nodes involved in the reward circuit, for example, in the posterior orbitofrontal cortex, subgenua l / subca llosa I cingulate, and nodes in and close to the diencephalon, in the brain stem including the hypothalamic neural pathways which lie in the deep brain to modulate hormone release, for example, for reproductive hormones, stress hormones, growth hormones, and oxytocin / vasopressin. The hypothalamus is a brain area that links the nervous system to the endocrine system. It produces various hormones, e.g. growth hormone, gonadotropin-releasing hormone (GnRH). Through hormonal and neural signaling, it communicates with the pituitary gland for release of hormones generated in the pituitary gland, such as the luteinizing hormone (LH) and follicle- stimulating hormone (FSH), which play important roles in reproduction. The hormones are regulated by internal signals from other organs or by external signals like stress. However, cognitive or behavioral stress can cause hormone dysfunction.Attorney Docket: 8350.2024-278WO

[0024] The device can stimulate deep brain neural pathways to modulate neural activity including stimulation of brain regions in the reward circuitry as well as stimulation of hypothalamus and hypothalamus-pituitary axis for hormone release. The minimally invasive and focused stimulation can target the desired pathways and minimize potential side effects. The feasibility of hormone modulation is implied through many studies. Electrical stimulation to the pituitary stalk in ex-vivo studies showed the vasopressin and oxytocin secretion. The pituitary could also be directly stimulated using this implant for hormone release. Also, changes in parameters could control their promotion and prevention of a particular hormone's secretion.

[0025] In one specific embodiment, the implant may be used to stimulate the hypothalamus to control precise release of the Gonadotropin-Releasing Hormone (GnRH). The non- invasive / minimally-invasive brain stimulation delivered by the implant disclosed herein can control the rate of release of GnRH, resulting in the subsequent release of testosterone aimed at improving alertness and reducing fatigue and anxiety.

[0026] In another embodiment, the implant could be used to deliver continuous stimulation to arrest neurodegeneration. In yet another embodiment, the implant could be used to stimulate nodes in the circuit of Papez, to activate memory pathways, and trigger nodes that can help improve executive function and / or degree of consciousness in patients suffering from related conditions, for example, those caused by traumatic brain injuries.

[0027] Most of the current prior art techniques utilize highly invasive deep-brain stimulation requiring an implant to be placed at the site of stimulation (e.g., techniques used toAttorney Docket: 8350.2024-278WO treat Parkinson's disease). No existing neurostimulation technique targets the hypothalamus for hormone release.

[0028] FIGS. 5(A-B) shows the device implanted in a cadaver, for determining the effectiveness of the implant. StereoEEG probes were used for measurement of electrical signals in the brain, and the sphenoid implant electrodes and circuitry are implanted in the sphenoid sinus. The device is capable of generating large fields in deep-brain regions for implants placed in the sphenoid sinus. The cadaver study showed that large, localized electric fields, sufficient to cause brain stimulation in deep brain regions, can be produced with small currents (5-10 mA), demonstrating the potential of the device and technique.

[0029] Many possible features of and variations of the device have been disclosed herein. As would be realized, any of these features or variations may be used in any combination. For example, the transducers may be configured to delivery different types of therapy on the same device, or to sense different responses from the brain. All possible combinations of features disclosed herein are contemplated to be within the scope of the invention.

Claims

Attorney Docket: 8350.2024-278WOClaims1. A transnasal implant comprising: a central portion comprising a means for powering the device and a circuitry for controlling delivery of therapy to the brain of a subject; and a plurality of spoked portions extending from the central portion, the spoked portions controlled by the circuitry for delivery of the therapy.2 The implant of claim 1 wherein the spoked portions are bidirectional and can be used for delivery of therapy and for measurement or signals generated by the brain of a subject.3 The implant of claim 1 further comprising: a plurality of transducers disposed at distal ends of each spoked portion. The implant of claim 3 wherein the transducers are electrodes for the delivery of electrical stimulation, the spoked portions further comprising: wiring from the circuitry for the delivery of electrical signals to the transducers.5 The implant of claim 3 wherein the transducers ultrasonic transducers for the delivery of ultrasonic energy, the spoked portions further comprising:Attorney Docket: 8350.2024-278WO wiring from the circuitry for the delivery of electrical signals to the transducers.

6. The implant of claim 3 wherein the transducers are optical transducers for the delivery of optical signals, the spoked portions further comprising: a waveguide disposed within the spoked portions for delivery of optical signals generated by the circuitry to the transducers and / or recording of optical signals measured.

7. The implant of claim 1, the spoked portions further comprising: a fluidic channel disposed within the spoked portions for the delivery of chemical therapy.

8. The implant of claim 1 wherein the spoked portions comprise coils for the delivery of magnetic field therapy, the spoked portions further comprising: wiring from the circuitry for the delivery of electrical signals to the coils.

9. The implant of claim 1 wherein the spoked portions are flexible.

10. The implant of claim 9, the spoked portions further comprising: a fluidic channel disposed within the spoked portions which can be pressurized with a fluid or with air to change the stiffness of the spoked portions.Attorney Docket: 8350.2024-278WO11. The implant of claim 10 wherein the fluidic channel extends into the central portion for changing the stiffness of the central portion.

12. The implant of claim 9, the spoked portions further comprising: an expandable wire mesh.

13. The implant of claim 9 wherein the spoked portions are composed of a flexible polymer.

14. The implant of claim 13 wherein the spoked portions are composed of polyimide, parylene or PDMS.

15. The implant of claim 1 wherein the spoked portion are composed of a rigid material.

16. The implant of claim 15 wherein the spoked portions are composed of acrylic or metal.

17. The implant of claim 1 wherein the central portion is implemented as a flexible printed circuit board.

18. A transnasal implant comprising: a central portion comprising a means for powering the device and a circuitry for controlling delivery of therapy to the brain of a subject;Attorney Docket: 8350.2024-278WO a plurality of spoked portions extending from the central portion; a plurality of electrical transducers disposed at the distal ends of the spoked portions for the delivery of electrical therapy to the brain of a subject; and wiring from the circuitry to each transducer for the delivery of electrical signals to the transducers.

19. A transnasal implant comprising: a central portion comprising a means for powering the device and a circuitry for controlling delivery of therapy to the brain of a subject; a plurality of spoked portions extending from the central portion, a plurality of optical transducers disposed at the distal ends of the spoked portions for the delivery of optical therapy to the brain of a subject; and a plurality of waveguides extending from the circuitry to the transducers for delivery of optical signals to the transducers.

20. A transnasal implant comprising: a central portion comprising a means for powering the device and a circuitry for controlling delivery of therapy to the brain of a subject; a plurality of spoked portions extending from the central portion, a plurality of ultrasonic transducers disposed at the distal ends of the spoked portions for the delivery of ultrasonic therapy to the brain of a subject; andAttorney Docket: 8350.2024-278WO wiring from the circuitry to each transducer for the delivery of electrical signals to the transducers.

21. A transnasal implant comprising: a central portion comprising a means for powering the device and a circuitry for controlling delivery of therapy to the brain of a subject; a plurality of spoked portions extending from the central portion, a plurality of chemical transducers disposed at the distal ends of the spoked portions for the delivery of chemical therapy to the brain of a subject; and a plurality of fluidic channels extending from the central portion to the transducers for delivery of chemicals to the transducers.

22. A transnasal implant comprising: a central portion comprising a means for powering the device and a circuitry for measuring activity of the deep brain and nearby structures of a subject; a plurality of spoked portions extending from the central portion, a plurality of sensors disposed at the distal ends of the spoked portions for recordings.

23. A transnasal implant comprising: a central portion comprising a means for powering the device and a circuitry for controlling delivery of therapy to the brain of a subject;Attorney Docket: 8350.2024-278WO a plurality of spoked portions extending from the central portion, wherein the spoked portions comprise coils; and wiring from the circuitry to each coil for the delivery of magnetic fields to the brain of the subject.

24. A transnasal implant comprising: a central portion comprising a means for powering the device and a circuitry for controlling delivery of therapy to the brain of a subject; and a plurality of spoked portions extending from the central portion, wherein the central portion and the plurality of spokes are encapsulated in a dissolvable capsule with the plurality of spokes folded into the disposable capsule under strain; and wherein the dissolvable capsule dissolves after implantation, thereby releasing plurality of spokes to an unfolded position.

25. A method comprising: inserting one or more of the transnasal implant of claim 1 into the sphenoid cavity of a subject; and controlling the transnasal implants via wired or wireless signals to control the delivery of electrical, optical, ultrasonic, chemical or magnetic field therapy to the brain of the subject.Attorney Docket: 8350.2024-278WO26. The method of claim 24 wherein parameters of the therapy are determined by software executing on a processor, the software including a machine learning component.

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