Neuromodulation involves stimulating nerves to alter nerve activity and is one of the most exciting emerging therapies for treatment of a broad range of diseases and conditions. For example, neuromodulation has potential to provide important and life changing therapy for intractable pain, spinal cord injuries, headaches Parkinson's disease, Alzheimer's disease, depression, and many other afflictions.
Some embodiments are directed to a system that includes a neuromodulator. The neuromodulator includes an electromagnetic (EM) wave generator configured to generate EM waves remote from a patient and to direct the EM waves to one or more target regions within the patient. Frequencies of the EM waves fall outside a range of frequencies that activates neurons. Intersection of the EM waves in each target region creates envelope-modulated electric and magnetic fields having one or more frequencies that fall within the range of frequencies that activates neurons. The neuromodulator includes control circuitry configured to control parameters of the EM waves produced by the EM wave generator.
According to some aspects, the system further includes a receiver configured to receive EM waves from the target region wherein the received EM waves are modulated by neural activity signals within the target region.
Some embodiments involve a process that includes generating electromagnetic (EM) waves at a location remote from a patient, wherein frequencies of the EM waves fall outside a range of frequencies that activate neurons. The EM waves are directed to one or more target region within the patient where they intersect. In each target region, intersection of the EM waves creates envelope-modulated electrical and magnetic fields having frequencies falling within the range of frequencies that activate neurons. The characteristics of the envelope-modulated electrical and magnetic fields can be altered by changing the parameters of the intersecting EM waves. The process may further include receiving EM waves modulated by a neural activity signal generated by neural activity within the target region.
The figures are not necessarily to scale. Like numbers used in the figures refer to like components. However, it will be understood that the use of a number to refer to a component in a given figure is not intended to limit the component in another figure labeled with the same number.
With an increasing trend of various forms of mental affliction among humans in present society, being able to sense and address parts of the brain on demand either to sense or stimulate or stimulate and simultaneously sense neural activity has important therapeutic consequences. Approaches discussed herein involve temporal interference phased-array stimulation and/or sensing (TIPS) that takes advantage of temporal interference between two electromagnetic (EM) waves to provide localized steerable neural interaction. Apart from a huge potential in treating and understanding mental illnesses, the approaches discussed herein provide an invaluable tool for researchers in neuroscience.
The neuromodulation devices disclosed herein can provide minimally-invasive and/or feedback-controlled neuromodulation and/or neural sensing within the brain and/or for peripheral nerves such as the vagus nerve or various other neural tissue in the body. The ability to selectively sense and/or stimulate nerve fascicles within a relatively small region enables treatment of a wide-range of peripheral and central nervous system disorders with targeted therapies.
Turning now to
The EM waves 281, 282 intersect within the target region 260. Linear superposition of the EM waves 281, 282 in the target region 260 causes a temporal variation in the electric and magnetic fields 270 in the target region 260 that differs from the temporal variation of the incident EM waves 281, 282. The linear superposition of the waves 281, 282 creates envelope-modulated electric and magnetic fields 270 in the target region 260. Modulation of the envelope occurs at a frequency which is a difference between the frequencies of the incident EM waves. The first EM wave 281 may be expressed mathematically as A1 sin w1(x), where A1 represents the amplitude of the first EM wave 281 and w1 represents the frequency of the EM wave 281. The second EM wave 282 may be expressed mathematically as A2 sin(1+α)w1(x), where A2 represents the amplitude of the second EM wave 282 and (1+α)w1 represents the frequency of the second EM wave 282. In the target region 260, the first and second EM waves combine to form envelope-modulated fields which can be expressed as A1 sin w1(x)+A2 sin(1+α)w1(x). Note that a could be negative.
For example,
Returning to
Each target region 260 may have volume of less than about 5 cm×5 cm×5 cm, or less than 125 cm3) or even less than about 30 cm3, or 2 cm×2 cm×2 cm, or less than about 8 cm3. In some embodiments, the controller 250 may control the parameters of the first and second EM waves 281, 282 such that a maximum amplitude of the envelope-modulated fields 270 fall within the target region 260. In some embodiments, the controller 250 may control the parameters of the first and second EM waves 281, 282 such that a maximum degree of modulation of the envelope-modulated fields 270 fall within the target region 260.
In some embodiments the EM waves 281, 282 that intersect within the target regions 260 are composites of multiple EM waves generated by the EM wave generator 210 of the neuromodulator 200. The neuromodulator 200 may comprise phased array that produces multiple EM waves that undergo constructive and/or destructive interference as they travel toward the patient. The controller 250 controls the parameters of the multiple EM waves, e.g., frequency, phase, and/or amplitude, generated by the phased array to beam steer and/or focus the intersecting EM waves to at least one target region 260.
In some implementations, the frequencies of the first and second EM waves 281, 282 may operate within FDA-approved WiFi bands, such as the 2.45 GHz frequency. These FDA-approved bands have been the subject of extensive research showing that these frequencies do not cause adverse reactions in people. In some embodiments, the frequencies of the EM waves 281, 282 may be greater than about 1 MHz and the frequencies of the envelope-modulated electric and magnetic fields are less than about 100 kHz. In some embodiments, the frequencies of the EM waves may be greater than about 150 kHz and frequencies of the envelope-modulated electric and magnetic fields are less than about 100 kHz.
The first EM wave 481 may be expressed mathematically as A1 sin w1(x), where A1 represents the amplitude of the first EM wave 481 and w1 represents the frequency of the EM wave 481. The second EM wave 482 may be expressed mathematically as A2 sin(1+α)w1(x), where A2 represents the amplitude of the second EM wave 482 and (1+α)w1 represents the frequency of the second EM wave 482. In the target region 461, the first and second EM waves 481, 482 combine to form envelope-modulated fields 471 which can be expressed as A1 sin w1(x)+A2 sin(1+α)w1(x).
The third EM wave 483 may be expressed mathematically as B1 sin w2(x), where B1 represents the amplitude of the second EM wave 483 and w2 represents the frequency of the EM wave 483. The fourth EM wave 484 may be expressed mathematically as B2 sin(1+β)w2(x), where B2 represents the amplitude of the second EM wave 484 and (1+β)w2 represents the frequency of the fourth EM wave 484. In the target region 462, the third and fourth EM waves 483, 484 combine to form envelope-modulated fields 472 which can be expressed as B1 sin w2(x)+B2 sin(1+β)w2(x).
As previously discussed, the controller 450 may control one or more parameters of one or more of the first, second, third, and fourth EM waves 481-484 to control characteristics of the envelope-modulated fields 471, 472 respectively created in the target regions 461, 462. Additionally or alternatively, using a phased array and the technique of constructive and destructive interference, the controller 450 may control one of more parameters of multiple EM waves generated by the neuromodulator to beam steer and/or focus the composite EM waves 481-484 to the target regions 461, 462.
In some embodiments, the parameters of the intersecting EM waves can be altered by the controller based on patient information provided to the controller.
The EM waves 681, 682 intersect within the target region 660. Linear superposition of the EM waves 681, 682 in the target region 660 causes a temporal variation in the electric and magnetic fields in the target region 660 that differs from the temporal variation of the incident EM waves 681, 682. The linear superposition of the waves 681, 682 creates envelope-modulated electric and magnetic fields 670 in the target region 660. Modulation of the envelope occurs at a frequency which is a difference between the frequencies of the incident EM waves 681, 682.
The neuromodulator 600 includes a controller 650 that can control parameters of the EM waves 681, 682, such as frequency, phase, and/or amplitude. Changing the parameters of the EM waves 681, 682 can be used to modify one or more characteristics of the envelope-modulated fields 670 in the target regions 660.
The controller 650 may be programmed to control the characteristics of the envelope-modulated fields 670 to provide a prescribed therapy or to achieve (or approach) a specific patent condition. For example, the controller 650 may change one or more of frequency, amplitude, and modulation depth of the envelope-modulated fields 670 by modifying the frequency, phase, and/or amplitude of the EM waves 681, 682.
According to some embodiments, the patient information device 641 comprises one or more sensors.
According to some embodiments, patient information may be obtained from a device 642 that provides a user interface which allows the patient or another operator to enter the patient information and/or record the patient response to a series of questions. The patient information entered may include measured values, e.g., heart rate, respiration rate, temperature, and/or may include subjective information, such as mood, perceived pain level, and/or other perceptions of psychological state, tracking and responding to certain visual or auditory stimuli in the field of view of the user.
One or both patient information devices 641, 642 may be configured to monitor dynamically changing physiological patient information, e.g., heart rate, respiration rate, blood pressure, body temperature, etc., and to communicate the patent information to the controller 650. In response, the controller 650 alters one or more parameters of the EM waves 681, 682 that create the envelope-modulated fields 670 within the target region 660. Components of the neuromodulator 600, e.g., the controller 650 and/or the patient information devices 641, 642 may synthesize and analyze both stimulation and sensing data by utilizing self-learning algorithms, and may be configured to adapt the EM waves 641, 642 in real-time to enhance therapeutic efficacy.
Based on the patient information obtained from devices 641, 642, the controller may develop a dynamic profile of biological conditions that occur in response to stimulation of the nerves within the target region 660. Optimal profiles of biological conditions that provide accurate feedback control for the neuromodulation function may be developed for each target region 660.
The approaches described with reference to
In addition to the “write-in” capability of the neuromodulator, a system may have “read-out” capability that allows monitoring of the neural activity within the target region. The neural activity within a target region can be read out when the neural activity within the target region modulates the envelope-modulated fields (also referred to as the interference signal) created by superposition of the EM waves in the target region. The modulation of the interference signal by neural activity results in EM waves that deviate from EM waves that are expected in the absence of neural activity. The EM waves are received at a receiver and the modulation caused by neural activity extracted from the received EM waves.
The interference signal is modulated by a neural activity signal generated by neural activity within the target region. The modulated interference signal is transmitted from the target region as a neural-activity-modulated EM wave. The neural-activity-modulated EM wave is received 760 by a receiver. Optionally the neural activity signal can be extracted 770 from the neural-activity-modulated EM wave and analyzed 780 to obtain information about the neural activity. Optionally, the neural activity signal can be used to control 790 neural stimulation at the target region and/or can be used to control other therapies and/or processes.
The EM waves 881, 882 intersect within the target region 860. Linear superposition of the EM waves 881, 882 in the target region 860 causes a temporal variation in the electric and magnetic fields 870 in the target region 260 that differs from the temporal variation of the incident EM waves 881, 882. The linear superposition of the waves 881, 882 creates envelope-modulated electric and magnetic fields, also referred to as the interference signal in the target region 860. Modulation of the interference signal occurs at a frequency which is a difference between the frequencies of the incident EM waves 881, 882.
The interference signal may be further modulated by a neural activity signal generated by neural activity in the target region. The neural activity may be stimulated by the interference signal, for example. The modulated interference signal is transmitted from the target region 860 as a neural-activity-modulated EM wave 824. The system 800 includes a receiver 823 configured to receive the neural-activity-modulated EM wave 824.
The system 800 includes a controller 850 coupled to the EM wave generator 811 and the receiver 823. The controller 850 can be configured to demodulate the received neural-activity-modulated EM wave 824 to extract the neural activity signal from the neural-activity-modulated EM wave 824. The controller 850 can be configured to control parameters of the EM waves 881, 882, such as frequency, phase, and/or amplitude. Changing the parameters of the EM waves 281, 882 can be used to modify one or more characteristics of the interference signal in the target regions 860. For example, the controller 850 may change one or more of frequency, amplitude, and modulation depth of the interference signal by modifying the frequency, phase, and/or amplitude of the EM waves 881, 882. In some implementations, the controller 850 may change the parameters of the EM waves 881, 882 based on the neural activity signal extracted from the neural-activity-modulated EM wave 824. For example, the controller 850 may change the characteristics of the interference signal, e.g., the amplitude and/or degree of modulation until the neural activity signal extracted from the neural-activity-modulated EM wave 824 indicates that a desired level of neural activity is being produced by the interference signal.
Although
The foregoing description of various embodiments has been presented for the purposes of illustration and description and not limitation. The embodiments disclosed are not intended to be exhaustive or to limit the possible implementations to the embodiments disclosed. Many modifications and variations are possible in light of the above teaching.
This application is a continuation of U.S. Ser. No. 16/235,634, filed Dec. 28, 2018, which is incorporated herein by reference in its entirety.
Number | Name | Date | Kind |
---|---|---|---|
3951134 | Malech | Apr 1976 | A |
5284144 | Delannoy et al. | Feb 1994 | A |
6646533 | Biegelson et al. | Nov 2003 | B2 |
6904323 | Samulski | Jun 2005 | B2 |
8306628 | Turner et al. | Nov 2012 | B2 |
8581783 | Higgins | Nov 2013 | B2 |
8702581 | Kraus et al. | Apr 2014 | B2 |
8834341 | Olree et al. | Sep 2014 | B2 |
8911342 | Dissing et al. | Dec 2014 | B2 |
8956273 | Mishelevich et al. | Feb 2015 | B2 |
8956274 | Schneider et al. | Feb 2015 | B2 |
9320911 | Szasz et al. | Apr 2016 | B2 |
9566426 | Simon et al. | Feb 2017 | B2 |
9999781 | Gale et al. | Jun 2018 | B2 |
10092769 | Scheinowitz et al. | Oct 2018 | B2 |
10173061 | Grossman et al. | Jan 2019 | B2 |
10188851 | Wenger et al. | Jan 2019 | B2 |
10307607 | Casse et al. | Jun 2019 | B2 |
20080284674 | Herz et al. | Nov 2008 | A1 |
20090018384 | Boyden et al. | Jan 2009 | A1 |
20100028647 | Burke | Feb 2010 | A1 |
20100256438 | Mishelevich | Oct 2010 | A1 |
20110199273 | Kim et al. | Aug 2011 | A1 |
20130096363 | Schneider et al. | Apr 2013 | A1 |
20140357935 | Ilmoniemi et al. | Dec 2014 | A1 |
20150080637 | Bonmassar et al. | Mar 2015 | A1 |
20150283395 | Sabouni | Oct 2015 | A1 |
20160023016 | Bonmassar et al. | Jan 2016 | A1 |
20160166843 | Casse et al. | Jun 2016 | A1 |
20170014637 | Basser | Jan 2017 | A1 |
20170225004 | Casse | Aug 2017 | A1 |
20170246481 | Mishelevich | Aug 2017 | A1 |
20190388020 | Stauch | Dec 2019 | A1 |
Number | Date | Country |
---|---|---|
102784436 | Nov 2012 | CN |
2975693 | Jan 2016 | EP |
2975694 | Jan 2016 | EP |
2288409 | Oct 2018 | EP |
2004064915 | Aug 2004 | WO |
2004082759 | Sep 2004 | WO |
Entry |
---|
Bonmassar et al., “Optimizing Microscopic Magnetic Fields for Neuronal Stimulation”, International Journal of Bioelectromagnetism, vol. 16, No. 1, 2014, pp. 1-31. |
Dmochowski et al., “Noninvasive Neuromodulation Goes Deep”, Cell, 169 (6), Jun. 2017, pp. 977-978. |
European Search Report from EP Application No. 19219898.4 dated Jun. 9, 2020, 7 pages. |
Ge et al., “A Design of Array Transcranial Magnetic Stimulation Coil System”, International Science Index, Biomedical and Biological Engineering, vol. 6, No. 5, 2012, 4 pages. |
Goats, :Interferential Current Therapy, Br. J. Sp. Med, vol. 24, No. 2, Jun. 1, 1990, pp. 87-92. |
Grossman et al., “Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields”, Cell, 169, Jun. 1, 2017, pp. 1029-1041. |
Rohde et al., “Focused High Frequency Repetitive Transcranial Magnetic Stimulation for Localisation of the Unexposed Primary Motor Cortex During Brain Tumour Surgery”, Journal of Neurology, Neurosurgery & Psychiatry, 2003; 74, 1283-1287. |
Number | Date | Country | |
---|---|---|---|
20220001173 A1 | Jan 2022 | US |
Number | Date | Country | |
---|---|---|---|
Parent | 16235634 | Dec 2018 | US |
Child | 17480861 | US |