Source: http://www.google.es/patents/US8538541
Timestamp: 2017-12-17 23:39:52
Document Index: 163814334

Matched Legal Cases: ['Application No. 2002223270', 'Application No. 2003283124', 'Application No. 2006211170', 'Application No. 2', 'Application No. 01994538', 'Application No. 01994538', 'Application No. 02774174', 'Application No. 02774174', 'Application No. 03702212', 'Application No. 03702212', 'Application No. 2007']

Patente US8538541 - Subthreshold stimulation of a cochlea - Google Patentes
An implantable apparatus, such as a cochlear implant, for delivering electrical plasticity informative stimuli to a neural network of an implantee. The apparatus comprises a stimulator device (40) that generates stimulation signals, and an electrode array (20) that receives the stimulation signals and...http://www.google.es/patents/US8538541?utm_source=gb-gplus-sharePatente US8538541 - Subthreshold stimulation of a cochlea
Número de publicación US8538541 B2
Número de solicitud US 10/494,995
Número de PCT PCT/AU2002/001537
También publicado como CA2466480A1, EP1450897A1, EP1450897A4, US20050033377, WO2003039660A1
Número de publicación 10494995, 494995, PCT/2002/1537, PCT/AU/2/001537, PCT/AU/2/01537, PCT/AU/2002/001537, PCT/AU/2002/01537, PCT/AU2/001537, PCT/AU2/01537, PCT/AU2001537, PCT/AU2002/001537, PCT/AU2002/01537, PCT/AU2002001537, PCT/AU200201537, PCT/AU201537, US 8538541 B2, US 8538541B2, US-B2-8538541, US8538541 B2, US8538541B2
Inventores Dusan Milojevic, John Parker
Citas de patentes (102), Otras citas (28), Citada por (1), Clasificaciones (10), Eventos legales (2)
US 8538541 B2
An implantable apparatus, such as a cochlear implant, for delivering electrical plasticity informative stimuli to a neural network of an implantee. The apparatus comprises a stimulator device (40) that generates stimulation signals, and an electrode array (20) that receives the stimulation signals and delivers the stimuli to the neural network of the implantee in response to the signals. The stimuli delivered to the implantee facilitates and/or controls the production and/or release of naturally occurring agents into the neural network to influence the functionality thereof.
1. An apparatus for delivering electrical stimuli to an auditory system of an implantee, comprising:
an stimulator configured to generate stimulation signals having the stimuli encoded therein; and
at least one electrode member configured to deliver the stimulation signals to the auditory system;
wherein the stimuli comprises plasticity informative stimuli having a magnitude below an auditory perception threshold of the implantee, the plasticity informative stimuli configured to facilitate the production and/or release of naturally occurring neurotrophic agents into the auditory system.
2. An apparatus of claim 1 wherein the apparatus is configured to modify the functionality of the auditory system in a predetermined manner.
3. An apparatus of claim 1 wherein the apparatus is configured to deliver the stimuli to at least one of the cochlea, inferior colliculus, the Subthalamic Nucleus (STN), the Globus Pallidus (GPi), and the Thalamus of the implantee.
4. An apparatus of claim 1 wherein the apparatus is a component of a hearing prosthesis that is also adapted to deliver auditory informative stimuli having a magnitude that is about at or above the auditory perception threshold of the implantee to the auditory system of the implantee.
5. An apparatus of claim 4 wherein the hearing prosthesis is a cochlear implant.
6. An apparatus of claim 4 wherein the hearing prosthesis is a hearing aid.
7. An apparatus of claim 4 wherein the prosthesis comprises an electrode array that is implantable in the cochlea of the implantee and is adapted to deliver said plasticity informative stimuli and auditory informative stimuli to the cochlea of the implantee.
8. An apparatus of claim 4 wherein the prosthesis comprises a first electrode array configured to deliver said plasticity informative stimuli and a second electrode array configured to deliver said auditory informative stimuli to the auditory system of the implantee.
9. An apparatus of claim 8 wherein the first electrode array is insertable into the auditory system at a location different from that of the second electrode array.
10. An apparatus of claim 8 wherein both said first and said second electrode arrays comprise an elongate carrier member having a plurality of electrodes mounted thereon.
11. An apparatus of claim 10 wherein the stimulator is electrically connected to each of the elongate carrier members via an electrical lead, the lead including one or more wires extending from each electrode of each elongate member.
12. An apparatus of claim 4 wherein the apparatus is implantable and further wherein the hearing prosthesis comprises an external component that is configured to operate in conjunction with the implantable apparatus, the external component comprising:
a microphone configured to detect sounds and further configured to output acoustic signals representative of said detected sounds; and
a processor configured to receive said acoustic signals from the microphone and to convert the signals into stimulation signals representative of the detected sounds, and further configured to encode said stimuli into said stimulation signals, deliver said stimulation signals transcutaneously to the stimulator.
13. An apparatus of claim 12 wherein the external component comprises a controller configured to control the output of the stimulator.
14. An apparatus of claim 12 wherein the external component further comprises a power source.
15. An apparatus of claim 1 wherein the apparatus is configured to deliver said plasticity informative stimuli to the cochlea of the implantee and is configured to operate in conjunction with a cochlear implant device adapted to deliver said auditory informative stimuli to the same cochlea of the implantee.
16. An apparatus of claim 1 wherein the apparatus is configured to operate in conjunction with an external component, the external component comprising a controller configured to control the output of the plasticity informative stimuli from the stimulator.
17. An apparatus of claim 16 wherein the external component further comprises a power source.
18. An apparatus of claim 1 wherein the stimulator is housed in a housing that is totally implantable within the implantee.
19. An apparatus of claim 18 wherein the housing is further configured to house a power source configured to provide the apparatus with at least sufficient power to deliver plasticity informative stimuli.
20. An apparatus of claim 1 wherein said at least one electrode member is part of an electrode array that is implantable in the auditory system of the implantee.
21. An apparatus of claim 20 wherein said electrode array comprises an elongate electrode carrier member having a plurality of electrodes mounted thereon.
22. An apparatus of claim 21 wherein the stimulator is electrically connected to the elongate member by way of an electrical lead, the lead comprising one or more wires extending from each electrode of the array mounted on the elongate member.
23. An apparatus of claim 1 wherein said plasticity informative stimuli is configured to be delivered in a duty cycle comprising a period of time (t1) of active stimulus and a period of time (t2) of no stimulus.
24. An apparatus of claim 23 wherein the apparatus has at least two electrode members and the plasticity informative stimuli is configured to be delivered simultaneously or sequentially by said at least two electrode members.
25. An apparatus of claim 24 wherein the beginning of the active part of the duty cycle for an electrode member is configured to occur with a delay with respect to the commencement of the duty cycle of at least one adjacent electrode member, but before the active part of the duty cycle of said at least one adjacent electrode member is finished.
26. An apparatus of claim 23 wherein the apparatus has at least two electrode members and wherein the active part of the duty cycle for each active electrode is configured to occur simultaneously.
27. An apparatus of claim 23 wherein the apparatus has at least two electrode members and wherein at any given time only one stimulating electrode is active.
28. An apparatus of claim 27 wherein the active part of each duty cycle is configured to be delivered sequentially by said at least two electrode members.
29. An apparatus of claim 1 wherein the apparatus is configured to measure the activity of one or more of the electrode members delivering auditory informative stimuli over a period of time of use.
30. An apparatus of claim 29 wherein the plasticity informative stimuli configured to be delivered by each electrode member is varied depending on the measure of activity determined for that electrode over said period of time.
31. An apparatus of claim 1 wherein the stimulator comprises a processor configured to process a set of instructions stored on the processor in the form of software.
32. An apparatus of claim 1 wherein said naturally occurring neurotrophic agents comprise one or more neurotrophic factors selected from the group comprising Brain Derived Neurotrophic Factor (BDNF), NGF, NT-3, NT-4/5, NT-6, LIF, GDNF, CNTF, and IGF-I.
33. An apparatus of claim 1 wherein said naturally occurring neurotrophic agents comprise neurotrophic factors that increase the survival of spiral ganglion cells.
34. An apparatus of claim 1 wherein said stimuli is configured to elicit outgrowth of spiral ganglion cells towards said at least one electrode member.
35. An apparatus of claim 1 wherein said stimuli is configured to be delivered at a frequency less than 5 kHz.
36. An apparatus of claim 1 wherein the apparatus is configured to deliver plasticity informative stimuli at times when the apparatus is not delivering auditory informative stimuli.
37. A method of delivering stimuli to an auditory system of an implantee, via an stimulator electrically coupled to at least one electrode member, wherein the electrode member is positioned to deliver the stimuli to the implantee, comprising:
generating stimulation signals having the stimuli to be delivered encoded therein; and
delivering said stimulation signals via at least one electrode member to the auditory system of the implantee;
wherein the stimuli comprises plasticity informative stimuli having a magnitude below an auditory perception threshold of the implantee and auditory informative stimuli, the plasticity informative stimuli configured to facilitate the production and/or release of naturally occurring neurotrophic agents into the auditory system.
38. A method of delivering stimuli to the auditory system of claim 37 wherein the stimuli is configured to modify the functionality of the auditory system in a predetermined desired manner.
39. A method of delivering stimuli to the auditory system of claim 37, further comprising:
positioning least one electrode member in a cochlea of the implantee prior to said delivering stimulation signals.
40. A method of delivering stimuli to the auditory system of claim 37 wherein said at least one electrode is adapted to deliver said plasticity informative stimuli and said auditory informative stimuli to the cochlea of the implantee.
41. An implantable apparatus for delivering electrical stimuli to an auditory system of an implantee, the apparatus comprising:
a stimulator configured to generate stimulation signals; and
an electrode array implantable in the auditory system, comprising at least one electrode member configured to deliver the stimulation signals to the auditory system;
wherein the stimuli comprises plasticity informative stimuli having a magnitude below a perception threshold of the implantee, the plasticity informative stimuli configured to facilitate the production and/or release of naturally occurring neurotrophic agents into the auditory system.
42. An implantable apparatus of claim 41 wherein the stimuli is configured to modify the functionality of the auditory system in a predetermined desired manner.
43. An implantable apparatus of claim 41 wherein the apparatus is configured to deliver the stimuli to at least one of the cochlea, inferior colliculus, the Subthalamic Nucleus (STN), the Globus Pallidus (GPi), and the Thalamus of the implantee.
44. An implantable apparatus of claim 41 wherein the perception threshold is an auditory perception threshold of the implantee.
45. An implantable apparatus of claim 41 wherein the apparatus is a component of a hearing prosthesis that is also adapted to deliver auditory informative stimuli having a magnitude that is about at or above the auditory perception threshold of the implantee to the auditory system of the implantee.
46. An implantable apparatus of claim 45 wherein the hearing prosthesis is a cochlear implant.
47. An implantable apparatus of claim 45 wherein the hearing prosthesis is a hearing aid.
48. An implantable apparatus of claim 45 wherein said electrode array is implantable in the cochlea of the implantee and is adapted to deliver said plasticity informative stimuli and said auditory informative stimuli to the cochlea of the implantee.
49. An implantable apparatus of claim 45 wherein the prosthesis comprises a first electrode array configured to deliver plasticity informative stimuli and a second electrode array configured to deliver auditory informative stimuli to the auditory system of the implantee.
50. An implantable apparatus of claim 49 wherein the first electrode array is insertable into the auditory system at a location different from that of the second electrode array.
51. An implantable apparatus of claim 44 wherein the apparatus is configured to deliver plasticity informative stimuli to the cochlea of the implantee and is configured to operate in conjunction with a cochlear implant device adapted to deliver auditory informative stimuli to the same cochlea of the implantee.
52. An implantable apparatus of claim 44 wherein the apparatus is configured to operate in conjunction with an external component, the external component comprising a controller that is configured to control the output of the plasticity informative stimuli from the stimulator.
53. An implantable apparatus of claim 44 wherein the stimulator is housed in a housing that is totally implantable within the implantee.
54. An implantable apparatus of claim 41 wherein the apparatus has at least two electrode members and the plasticity informative stimuli is configured to be delivered simultaneously or sequentially by said at least two electrode members.
55. An implantable apparatus of claim 41 wherein the apparatus has at least two electrode members and wherein the active part of the duty cycle for each active electrode is configured to occur simultaneously.
56. An implantable apparatus of claim 41 wherein the apparatus has at least two electrode members and wherein at any given time only one stimulating electrode is active.
57. An implantable apparatus of claim 41 wherein said naturally occurring neurotrophic agents comprise one or more neurotrophic factors selected from the group comprising Brain Derived Neurotrophic Factor (BDNF), NGF, NT-3, NT-4/5, NT-6, LIF, GDNF, CNTF, and IGF-I.
58. An implantable apparatus of claim 41 wherein said naturally occurring neurotrophic agents comprise neurotrophic factors that increase the survival of spiral ganglion cells.
59. An implantable apparatus of claim 41 wherein said stimuli is configured to elicit outgrowth of spiral ganglion cells towards said at least one electrode member.
60. An implantable apparatus of claim 41 wherein the apparatus is configured to deliver plasticity informative stimuli at times when the apparatus is not delivering auditory informative stimuli.
61. A method of delivering stimuli to an auditory system of an implantee via an electrode array having at least one electrode member, configured to deliver the stimuli to the implantee and positioned in a neural network, comprising:
delivering said stimulation signals to said via at least one electrode member to the implantee;
wherein the stimuli includes plasticity informative stimuli having a magnitude below a perception threshold of the implantee, the plasticity informative stimuli configured to facilitate the production and/or release of naturally occurring neurotrophic agents into the neural network.
62. A method of delivering stimuli to the neural network of claim 61 wherein the stimuli is configured to modify the functionality of the neural network in a predetermined desired manner.
63. A method of delivering stimuli to the neural network of claim 61 wherein the stimuli is configured to be delivered to the auditory system of the implantee.
64. A method of delivering stimuli to the neural network of claim 61 wherein positioning an electrode array comprises positioning said electrode array in a cochlea of the implantee.
65. A method of delivering stimuli to the neural network of claim 61 wherein said at least one electrode is adapted to deliver plasticity informative stimuli and auditory informative stimuli to the cochlea of the implantee.
66. An implantable apparatus for delivering electrical stimuli to a neural network of an implantee, the apparatus comprising:
at least one electrode member configured to receive the stimulation signals and configured to deliver the stimuli to the neural network in response to said signals;
wherein the stimuli includes plasticity informative stimuli having a magnitude below a perception threshold of the implantee, the plasticity informative stimuli facilitating the production and/or release of naturally occurring neurotrophic agents into the neural network, and
wherein said naturally occurring neurotrophic agents comprise one or more neurotrophic factors selected from the group comprising Brain Derived Neurotrophic Factor (BDNF), NGF, NT-3, NT-4/5, NT-6, LIF, GDNF, CNTF, and IGF-I.
67. An implantable apparatus of claim 66 wherein the apparatus is configured to deliver stimuli to the auditory system of the implantee.
68. An implantable apparatus of claim 67 wherein the perception threshold is an auditory perception threshold of the implantee.
69. An implantable apparatus of claim 68 wherein the apparatus is a component of a hearing prosthesis that is also adapted to deliver auditory informative stimuli having a magnitude that is about at or above the auditory perception threshold of the implantee to the auditory system of the implantee.
70. An implantable apparatus of claim 69 wherein the hearing prosthesis is a cochlear implant.
71. An implantable apparatus of claim 69 wherein the hearing prosthesis is a hearing aid.
72. An implantable apparatus of claim 69 wherein the prosthesis includes an electrode array that is implantable in the cochlea of the implantee and is adapted to deliver both plasticity informative stimuli and auditory informative stimuli to the cochlea of the implantee.
73. An implantable apparatus of claim 69 wherein the prosthesis comprises a first electrode array configured to deliver plasticity informative stimuli and a second electrode array configured to deliver auditory informative stimuli to the auditory system of the implantee.
74. An implantable apparatus of claim 68 wherein the apparatus delivers plasticity informative stimuli to the cochlea of the implantee and is configured to operate in conjunction with a cochlear implant device adapted to deliver auditory informative stimuli to the same cochlea of the implantee.
75. An implantable apparatus of claim 66 wherein the apparatus is configured to deliver the stimuli to at least one of the cochlea, inferior colliculus, the Subthalamic Nucleus (STN), the Globus Pallidus (GPi), and the Thalamus of the implantee.
76. An implantable apparatus of claim 75 wherein said naturally occurring neurotrophic agents comprise neurotrophic factors that increase the survival of spiral ganglion cells.
77. An implantable apparatus of claim 66 wherein the apparatus has at least two electrode members and the plasticity informative stimuli is configured to be delivered simultaneously or sequentially by said at least two electrode members.
78. An implantable apparatus of claim 66 wherein the apparatus has at least two electrode members and wherein at any given time only one stimulating electrode is active.
79. An implantable apparatus of claim 66 wherein said stimuli elicits outgrowth of spiral ganglion cells towards said at least one electrode member.
80. A method of delivering stimuli to an auditory system of an implantee, via an stimulator electrically coupled to at least one electrode member, wherein the electrode member is positioned to deliver the stimuli to the implantee, comprising the steps of:
wherein the stimuli includes plasticity informative stimuli having a magnitude below a perception threshold of the implantee, the plasticity informative stimuli facilitating the production and/or release of naturally occurring neurotrophic agents into the auditory system, wherein said naturally occurring neurotrophic agents comprise one or more neurotrophic factors selected from the group comprising Brain Derived Neurotrophic Factor (BDNF), NGF, NT-3, NT-4/5, NT-6, LIF, GDNF, CNTF, and IGF-I.
81. A method of delivering stimuli to the auditory system of claim 80 wherein the stimuli is configured to be delivered to the auditory system of the implantee.
82. A method of delivering stimuli to the auditory system of claim 80 wherein positioning at least one electrode member comprises positioning said at least one electrode member in a cochlea of the implantee.
83. A method of delivering stimuli to the auditory system of claim 80 wherein said at least one electrode is adapted to deliver plasticity informative stimuli and auditory informative stimuli to the cochlea of the implantee.
84. An implantable apparatus for delivering electrical stimuli to a neural network of an implantee, the apparatus comprising:
a stimulator that generates stimulation signals; and
wherein said naturally occurring neurotrophic agents comprise neurotrophic factors that increase the survival of spiral ganglion cells.
85. An implantable apparatus of claim 84 wherein the apparatus delivers stimuli to the auditory system of the implantee.
86. An implantable apparatus of claim 85 wherein the perception threshold is an auditory perception threshold of the implantee.
87. An implantable apparatus of claim 86 wherein the apparatus is a component of a hearing prosthesis that is also adapted to deliver auditory informative stimuli having a magnitude that is about at or above the auditory perception threshold of the implantee to the auditory system of the implantee.
88. An implantable apparatus of claim 87 wherein the hearing prosthesis is a cochlear implant.
89. An implantable apparatus of claim 87 wherein the hearing prosthesis is a hearing aid.
90. An implantable apparatus of claim 86 wherein the apparatus delivers plasticity informative stimuli to the cochlea of the implantee and is configured to operate in conjunction with a cochlear implant device adapted to deliver auditory informative stimuli to the same cochlea of the implantee.
91. An implantable apparatus of claim 86 wherein the apparatus is configured to operate in conjunction with an external component, the external component comprising a controller that controls the output of the plasticity informative stimuli from the stimulator.
92. An implantable apparatus of claim 84 wherein the apparatus is configured to deliver the stimuli to at least one of the cochlea, inferior colliculus, the Subthalamic Nucleus (STN), the Globus Pallidus (GPi), and the Thalamus of the implantee.
93. An implantable apparatus of claim 84 wherein the apparatus has at least two electrode members and the plasticity informative stimuli is configured to be delivered simultaneously or sequentially by said at least two electrode members.
94. An implantable apparatus of claim 84 wherein the apparatus has at least two electrode members and wherein the active part of the duty cycle for each active electrode occurs simultaneously.
95. An implantable apparatus of claim 84 wherein the apparatus has at least two electrode members and wherein at any given time only one stimulating electrode is active.
96. An implantable apparatus of claim 84 wherein said naturally occurring neurotrophic agents comprise one or more neurotrophic factors selected from the group comprising Brain Derived Neurotrophic Factor (BDNF), NGF, NT-3, NT-4/5, NT-6, LIF, GDNF, CNTF, and IGF-I.
97. An implantable apparatus of claim 84 wherein said stimuli elicits outgrowth of spiral ganglion cells towards said at least one electrode member.
98. A method of delivering stimuli to an auditory system of an implantee, via an stimulator electrically coupled to at least one electrode member, wherein the electrode member is positioned to deliver the stimuli to the implantee, comprising the steps of:
delivering said stimulation signals via at least one electrode member to the implantee;
wherein the stimuli includes plasticity informative stimuli having a magnitude below a perception threshold of the implantee, the plasticity informative stimuli facilitating the production and/or release of naturally occurring neurotrophic agents into the auditory system, wherein said naturally occurring agents comprise neurotrophic factors that increase the survival of spiral ganglion cells.
99. A method of delivering stimuli to the auditory system of claim 98 wherein the stimuli is configured to be delivered to the auditory system of the implantee.
100. A method of delivering stimuli to the auditory system of claim 98 wherein positioning at least one electrode member comprises positioning said at least one electrode member in a cochlea of the implantee.
101. A method of delivering stimuli to the auditory system of claim 98 wherein said at least one electrode is adapted to deliver plasticity informative stimuli and auditory informative stimuli to the cochlea of the implantee.
102. An implantable apparatus for delivering electrical stimuli to a neural network of an implantee, the apparatus comprising:
wherein said stimuli elicits outgrowth of spiral ganglion cells towards said at least one electrode member.
103. An implantable apparatus of claim 102 wherein the apparatus delivers stimuli to the auditory system of the implantee.
104. An implantable apparatus of claim 103 wherein the perception threshold is an auditory perception threshold of the implantee.
105. An implantable apparatus of claim 102 wherein the wherein the apparatus is configured to deliver the stimuli to at least one of the cochlea, inferior colliculus, the Subthalamic Nucleus (STN), the Globus Pallidus (GPi), and the Thalamus of the implantee.
106. An implantable apparatus of claim 102 wherein the hearing prosthesis is a cochlear implant.
107. An implantable apparatus of claim 102 wherein the hearing prosthesis is a hearing aid.
108. An implantable apparatus of claim 102 wherein the apparatus has at least two electrode members and the plasticity informative stimuli is configured to be delivered simultaneously or sequentially by said at least two electrode members.
109. An implantable apparatus of claim 102 wherein the apparatus has at least two electrode members and wherein at any given time only one stimulating electrode is active.
110. An implantable apparatus of claim 102 wherein said naturally occurring neurotrophic agents comprise one or more neurotrophic factors selected from the group comprising Brain Derived Neurotrophic Factor (BDNF), NGF, NT-3, NT-4/5, NT-6, LIF, GDNF, CNTF, and IGF-I.
111. An implantable apparatus of claim 102 wherein said naturally occurring neurotrophic agents comprise neurotrophic factors that increase the survival of spiral ganglion cells.
112. A method of delivering stimuli to an auditory system of an implantee, via an stimulator electrically coupled to at least one electrode member, wherein the electrode member is positioned to deliver the stimuli to the implantee, comprising the steps of:
wherein the stimuli includes plasticity informative stimuli having a magnitude below a perception threshold of the implantee, the plasticity informative stimuli facilitating the production and/or release of naturally occurring neurotrophic agents into the auditory system, wherein said stimuli elicits outgrowth of spiral ganglion cells.
113. A method of delivering stimuli to a neural network of claim 112 wherein the stimuli provided by the stimulation signals is configured to be delivered to the auditory system of the implantee.
This application claims the priority of and is a national stage application of PCT Application No. PCT/AU02/01537, entitled, “Subthreshold Stimulation of a Cochlea,” filed on Nov. 11, 2002, which claims the priority of Australian Provisional Application No. PR 8797, filed on Nov. 9, 2001. The entire contents and disclosures of the above applications are hereby incorporated by reference.
The axon is a cell structure specialised for intracellular transfer of information over long distances. An axon originates at a cone-shaped thickening on the cell body called the axon hillock. Information is transmitted within neurons via electrical signals. Such electrical signals are represented by the action potential, which is a single, transient reversal of membrane polarity. The action potential is the basic unit of signalling in the neural system. The intracellular information transfer is carried out by conduction of the action potential along the axon and this conducting mechanism is known as saltatory conduction.
The synaptic terminal is situated at the opposite end of the axon. The synaptic terminal contains synaptic vesicles, which play an important role in interneural communication.
In a typical chemical synapse, a branch of the afferent or presynaptic axon swells at its terminus to form a bouton, which is very close to, but does not actually physically touch the specialised postsynaptic side of the synapse. Most neurons have a dendrite that is capable of responding to a chemical signal transmitted from the presynaptic axon. The gap between the two communicating neurons is typically 20 nm wide and is called the synaptic cleft. The fluid-filled gap between the two neurons prevents the direct transfer of electrical current from one neuron to another. The signal transfer between the neurons is instead carried out by rapid diffusion of naturally occurring chemicals called neurotransmitters. The molecules comprising the neurotransmitters in a presynaptic neuron are contained within synaptic vesicles. The signal transmission occurs by synaptic vesicles fusing with the cell membrane of the presynaptic neuron, excreting the neurotransmitters molecules to the cleft which than rapidly diffuse and interact with the postsynaptic neuron where it may produce either an excitatory or inhibitory postsynaptic potential.
2. Import that information into its brain where it can be processed; and
3. Generate a behavioural response.
The peripheral auditory system is subdivided into the external ear, the middle ear, and the inner ear. The external ear collects the sound energy as pressure waves which are converted to mechanical motion of the eardrum. This motion is transformed across the middle ear and transferred to the inner ear, where it is frequency analysed and converted into neural codes that are carried by the eighth cranial nerve, ie. the auditory nerve, to the central auditory system.
An apparatus for delivering random patterns of activation to the auditory nerve to generate psuedospontaneous activity in the nerve is described in U.S. Pat. No. 6,295,472. While this system is described as useful for treating tinnitus, the patent does not describe use of an apparatus that delivers stimulation in a manner that controls the production and/or release of naturally occurring agents into the auditory system.
The efficiency and potential benefits that the cochlear implant may provide heavily depend on the plasticity of the neural system of the implantee. For example, it is well known that efficiency of the implant decreases as the length of deafness, particularly in prelingually deaf people, increases.
Some other examples where neural rearrangements occur as a consequence of an injury or treatment of the injury include, but are not limited to, visual impairment, sensorineural and motorneural injuries. Further, the device may be used to treat abnormal functionality of part of a neural system. Sensorineural and motorneural abnormalities, such as depression, Parkinson's disease, Alzheimer's disease may also be treated with the herein described device. These diseases may be treated at present with naturally occurring agents, administered to a patient through a mechanism(s) other than electrical stimulation, e.g. oral administration of agents in a form of a tablet.
According to one aspect, the present invention is an implantable apparatus for delivering electrical stimuli to a neural network of an implantee, the apparatus comprising:
a stimulator device that generates stimulation signals; and
at least one electrode member that receives the stimulation signals and delivers said stimuli to the neural network in response to said signals;
wherein the stimuli facilitates and/or controls the production and/or release of naturally occurring agents into the neural network to influence the functionality thereof.
In a further aspect, the present invention is an implantable apparatus for making desired modifications to the functionality of a neural network of an implantee, the apparatus comprising:
As used herein, the term “neural network” is to be understood as including the entire nervous system of the implantee, including the peripheral and central nervous systems.
The stimuli delivered by the apparatus can comprise plasticity informative stimuli having a magnitude below the auditory perception threshold of the implantee.
In a still further embodiment, the apparatus can be a component of a hearing prosthesis that is also adapted to deliver auditory informative stimuli having a magnitude that is about at or above the auditory perception threshold of the implantee to the auditory system of the implantee.
In a further embodiment, both said first and said second electrode arrays can comprise an elongate carrier member having a plurality of electrodes mounted thereon. The stimulator device can be electrically connected to each of the elongate carrier members by way of an electrical lead, the lead including one or more wires extending from each electrode of each elongate member.
In a still further embodiment, the hearing prosthesis can include an external component that works in conjunction with the implantable apparatus, the external component comprising:
a microphone that detects sounds and outputs acoustic signals representative of said detected sounds;
a processor that receives said acoustic signals from the microphone and converts the signals into stimulation signals representative of the detected sounds that are then delivered transcutaneously to the stimulator device.
When the apparatus is delivering stimuli to the cochlea, the electrical stimulation can have a magnitude less than the auditory perception threshold of the implantee that is hereinafter termed “plasticity informative stimuli” or a magnitude about equal to or greater than the auditory perception threshold of the implantee that is hereinafter termed “auditory informative stimuli”. The apparatus can be adapted to deliver both types of stimuli to the implantee.
Similarly, when the apparatus is delivering stimuli to the visual system, the electrical stimulation can have a magnitude less than the visual perception threshold of the implantee that is hereinafter termed “plasticity informative stimuli” or a magnitude about equal to or greater than the visual perception threshold of the implantee that is hereinafter termed “visual informative stimuli”. The apparatus can be adapted to deliver both types of stimuli to the implantee.
In one embodiment, said naturally occurring agents can comprise one or more neurotrophic factors or neurotrophins. In one embodiment, one of the neurotrophic factors can comprise Brain Derived Neurotrophic Factor (BDNF).
In another embodiment, the neurotrophic factors can be selected from the group comprising, but not limited to, NGF, NT-3, NT4/5, NT-6, LIF, GDNF, CNTF, and IGF-1.
Neurotrophic factors are a key element in establishment and maintenance of synapses. Neurotrophins secreted by the postsynaptic cell are likely to be highly localised owing to their propensity to bind to the cell surface near the secretion site. Endogenous neurotrophins, secreted in response to synaptic activity, induce the morphological changes that lead to the maintenance of the existing synapses or formation of new synaptic contacts. In the absence of signals, synaptic contacts may disconnect, breaking the particular neural pathway. Synaptic action of neurotrophins consists of two modes. In a resting “permissive” mode, neurotrophins are secreted at a low level through constitutive secretion or regulated secretion triggered by subthreshold and low-frequency synaptic activity. This permissive mode provides trophic regulation of synaptic functions, including the ability to generate long-term potentiation. In the active “instructive” mode, neurotrophic factors are secreted as a higher level of response to intense synaptic activity that results in a transient high-level calcium concentration in the post-synaptic cytoplasm. The secretion of neurotrophins may be supplemented by activity-dependent synthesis and transport of neurotrophins. The high level of neurotrophins then induce the modification of synaptic functions and the formation of new synaptic contacts.
1. Individual cells, e.g. spiral ganglion cells;
2. Pairs of cells connected by synapses, e.g. cochlear nucleus;
3. Networks of interacting cells, e.g. nucleus of the lateral leminiscus or inferior colliculus; and
2. Pairs of cells connected by synapses, e.g. cochlear nucleus (by e.g. ABI);
3. Networks of interacting cells, e.g. nucleus of the lateral leminiscus or inferior colliculus (e.g. MBI); and
The plasticity informative stimuli is preferably delivered to the cochlea at a frequency less than 5 kHz, more preferably less than 2 kHz, and still more preferably much lower than this frequency. In one embodiment, the frequency can be between 1 and 100 Hz. In another embodiment the frequency can be between 10 and 100 Hz. In another embodiment, the frequency can be between 20 and 100 Hz. In another embodiment the frequency can be about 50 Hz.
In a further embodiment, the delivery of plasticity informative stimuli can occur at times when the apparatus is incapable of or is not delivering auditory informative stimuli. For example, the delivery of plasticity informative stimuli can occur when the implantee is asleep and not using the apparatus for the delivery of auditory informative stimuli.
As described above, the apparatus can comprise a cochlear implant. As described, a cochlear implant bypasses the hair cells in the cochlea and directly delivers electrical stimulation to the auditory nerve fibres, thereby allowing the brain to perceive a hearing sensation resembling the natural hearing sensation normally delivered to the auditory nerve. U.S. Pat. No. 4,532,930, the contents of which are incorporated herein by reference, provides a description of one type of cochlear implant system that could be modified to deliver the plasticity informative stimuli.
In one embodiment, the system can have an implantable unit comprising:
(a) a power source that provides the power requirements of the implantable unit.
The microphone can be a directional dual cavity microphone or a single cavity microphone. A dual-cavity microphone provides an effective means of rejecting common mode body-conducted noise emanating from body functions, such as chewing, respiration and blood flow.
Preferably, the microphone of the totally implantable system will function at a pressure ranging from 1.5 atm 0.7 atm. This allows a wearer to still use the implant system while recreational diving or during flights on commercial or light aircraft or at elevated locations. The microphone will preferably still operate after being subject to a pressure outside the above range. Preferably, the microphone will survive any exposure to a pressure in the 5 atm to 0.5 atm range.
A stiffening element, such as a metallic stylet or bioresorbable stiffening element can be used to bias the elongate member into said first configuration. On implantation, the stylet can be withdrawn or the stiffening element can dissolve, or at least soften, to allow the carrier member to adopt its preferred second configuration.
In one embodiment, the lead can extend from the elongate member to the stimulator device or at least the housing thereof. In one embodiment, the lead is continuous with no electrical connectors, at least external the housing of the stimulator device, required to connect the wires extending from the electrodes to the stimulator device. One advantage of this arrangement is that there is no requirement for the surgeon implanting the device to make the necessary electrical connection between the wires extending from the electrodes and the stimulator device. Electrical connection between the processor device within the housing and the electrode array and the one or more extracochlea electrodes can also be provided by respective hermetic and insulated ceramic feedthroughs. Each feedthrough can be formed using the method described in U.S. Pat. No. 5,046,242, the contents of which are incorporated herein by reference.
In this regard, the electronics housed in the implantable unit is provided with a clock, controlling the overall operation of the device. This clock can control the timing with which the predetermined stimulation pattern can occur. This clock can be programmable to operate in “real time” such that the recipient can receive plasticity informative stimuli at times when the recipient is asleep or not receiving auditory informative stimuli. Such a clock would ideally take into consideration time changes and personal settings, such as shift work etc, and would therefore be controllable through an external device, such as a conventional external speech processor.
(iii) at least one electrode member that receives the stimulation signals and delivers said stimuli to the auditory system of the implantee in response to said signals;
wherein the stimuli facilitates and/or controls the production and/or release of naturally occurring agents into the auditory system of the implantee to influence the neural plasticity thereof.
In this and other aspects, the stimulator device can be adapted to monitor or detect when the at least one electrode member is not delivering auditory informative stimuli. On monitoring or detecting that no auditory informative stimuli is being delivered by the electrode member, the apparatus can commence delivery of plasticity informative stimuli.
In a further embodiment of this and other aspects, the apparatus can detect when transcutaneous signals from an external controller have stopped, such as due to deactivation of the external controller or removal from the implantee, and so commence delivery of plasticity informative stimuli. In this regard, the stimulator device can be adapted to delay delivery of plasticity informative stimuli until a predetermined time period since delivery of the last auditory informative stimuli. The time period can be, for example, in the range of a few seconds to hours as prescribed by a clinician or other person responsible for the maintenance and functioning of the apparatus. Such persons may include medical practitioners, audiologists, and hearing prosthesis engineers.
In a still further embodiment, the carrier member on at least implantation into the auditory system can have a delivery mechanism that delivers appropriate agents, preferably naturally occurring agents or agents controlling and/or facilitating the production and/or release of naturally occurring agents. In one embodiment, the agents can be neurotrophic factors.
(1) the desired agent which acts on the auditory system, or
The delivery mechanism may be in the form of a coating, comprising a slow-releasing film containing neurotrophic factors. It is considered that such an initial dose of neurotrophic or other factors may be required to initiate the cell response which will be then maintained by electrical stimulation. In addition or instead, the carrier member can be used to deliver neurotrophic factors to the site of implantation of the carrier member. In this regard, the implant can further comprise a fluid reservoir and pumping device that is adapted to pump neurotrophic factors out of the carrier member and into the auditory system.
Further, the agent can be added in an acute manner during the surgical procedure, where the device does not feature any additional component to those previously described. The agent is, for example, added by injection during surgery.
In one embodiment, the plasticity informative stimuli is preferably delivered in a duty cycle comprising a period of time (t1) of active stimulus and a period of time (t2) of no stimulus. The period of time (t1) preferably comprises a relatively short period of time of relatively high frequency stimulus (active part) followed by a relatively long period of time (t2) of no activity (inactive part), ie. t1<t2, where t1:t2 is at least about 0.2 or smaller. In this embodiment, t1 can be in the range of about 0.001 seconds to about 100 seconds.
As mentioned, the total period of time between two stimulations (t1+t2) is defined as a duty cycle. In this embodiment, the duty cycle is the basic unit of a plasticity informative stimulus. The nature and repetition rate of the duty cycle can preferably be prescribed by the clinician responsible for the implantee's apparatus. In one embodiment, the duty cycles can be repeated, for each individual channel, in a sequence t1-t2, t1-t2, t1-t2, t1-t2 and so on. In another embodiment, a pause can be provided between duty cycles. The length of the pause can be variable. For example only, a number of duty cycles can be applied in a sequence as shown previously (t1-t2, t1-t2, t1-t2, t1-t2). Then, each of group of such a plurality of cycles can be separated by a pause (a period of non-activity) t3. For example:
(t1-t2, t1-t2, t1-t2, t1-t2)-t3-(t1-t2, t1-t2, t1-t2, t1-t2)-t3-(t1-t2, t1-t2, t1-t2,t1-t2)-t3-(t1-t2, t1-t2, t1-t2, t1-t2)
In this case, t3 is preferably significantly longer than either of t1 or t2. It will be appreciated that any combination of the duty cycles and pauses between them could be utilised by the present invention as thought appropriate by the consulting clinician.
It is envisaged that the plasticity informative stimuli may feature one and only duty cycle (DC). Alternatively, the plasticity informative stimuli can feature more then one duty cycle. Any combination of two or more duty cycles is possible, eg.:
DC1-DC1-DC1-DC1-LP-DC2-DC2-DC2-DC2
where LP=long pause that is longer than DC1 or DC2; or
For simplicity in all cases the cochlea is divided into the basal part and apical part but the plasticity informative stimuli and/or agents can be delivered in a much larger number of sectors. Effectively, as far as plasticity informative stimuli is concerned, a total number of stimulating pads+a total number of virtual channels determines the maximum number of independent sectors that the plasticity informative stimuli can be delivered to.
In another example, the apparatus measures the activity of one or more of the stimulating electrodes delivering auditory informative stimuli over a period of use, such as a day. For example, the apparatus can measure the frequency of stimulation, the stimulation current, and/or the neural response for each of stimulating electrodes. In this case, the apparatus can, for example, measure the different level of activity during the day exhibited by each of the electrodes and so provide a measure of the activity and/or the differences therebetween of the auditory fibres located along the cochlea.
In this case, the plasticity informative stimuli delivered by each electrode can be varied depending on the measure of activity determined for that electrode over the preceding time period. The delivery of the plasticity informative stimuli can be varied such that the overall stimulation received by the auditory fibres from any particular electrode over a predetermined period of time is substantially equal or the same as other auditory fibres receiving stimulation from other electrodes in the array.
In such circumstances, an algorithm may be used to control electrical stimulation carrying plasticity informative stimuli. For any stimulating electrode, N0 delivering auditory informative stimuli, a corresponding weighting function W0 could be calculated according to:
W 0=Σ(Ti×Ei×Ni), i being between 1 and n
n is a total number of stimulating electrodes;
N0 is the stimulating electrode for which weight is being calculated;
Ti is time of stimulus;
Ei is amplitude of stimulus; and
Ni is contribution factor for the particular electrode; N0 has the strongest contribution and electrodes positioned further from N0 have decreasing contribution but not necessarily in a uniformly decreasing manner.
Wp 0=Σ(Tpi×Epi×Npi), i being between 1 and n
Epi is amplitude of stimulus; and
Npi is contribution factor for the particular electrode; N0 has the strongest contribution and electrodes positioned further from N0 have decreasing contribution but not necessarily in a uniformly decreasing manner.
In this way, the effect of direct stimulation is taken into account as well as the stimulation delivered by adjoining stimulating electrodes. The “auditory” probability (Pa) for each particular stimulating electrode to deliver plasticity informative stimuli is then a function of the weight (Wi) of auditory informative stimuli, Pai=f(Wi). The function that relates the weight of auditory informative stimuli and probability of delivering plasticity informative stimulus is complex. Further, the “plasticity” probability (Pp) for each particular stimulating electrode to deliver plasticity informative stimuli is then a function of the weight (Wpi) of plasticity informative stimuli, Ppi=f(Wpi).
P=f(Pa,Pp)
In a still further embodiment, the system monitors the activity of the electrodes and determines the weight of the auditory informative stimuli, similar to the above formula. The probability of the stimulating electrode delivering plasticity informative stimuli can be inversely proportional to the auditory informative stimuli weight Wx. The result is that the longer the period of time a neuron spends without being active (firing), the higher the probability that that stimulating electrode will deliver plasticity informative stimuli to the auditory system, Pxi=f(1N/Wi), Wxi=f(txi), where Pxi is the probability of delivering plasticity informative stimuli, related to a period of auditory informative stimulus inactivity, Wxi is the weight of auditory informative stimuli and is proportional to the period of time without auditory informative stimuli txi.
P=f{(c a(PIVTF) ×P a(PIVTF)),(c a(NRT PIVTF) ×P a(NRT PIVTF)),(cp(PIVTF) ×P p(PIVTF)),(c p(NRT PIVTF) ×P p(NRT PIVTF))}
c is a contributing coefficient for each of the probabilities;
Index PIVTF is related to input received from a function hereinafter called “Plastic Informative Variable Tracking Function”; and
Index NRT PIVTF is related to input received from a NRT-based Plastic Informative Variable Tracking Function.
(iii) transmitting said signals to said at least one electrode member; and
(iv) delivering said stimuli in response to said signals;
wherein the stimuli facilitates and/or controls the production and/or release of naturally occurring agents into the neural network to influence the neural plasticity thereof.
In this aspect, step (i) preferably comprises positioning said at least one electrode member such that it is positioned in an auditory system of an implantee, such as the cochlea. In this embodiment, the at least one electrode is also preferably adapted to deliver auditory informative stimuli to the cochlea of the implantee. In another embodiment of this aspect, auditory informative stimuli may be delivered by a hearing prosthesis other than a cochlear implant, such as a middle ear implant (MEI) or a hearing aid (HA).
In this aspect, the method of delivering plasticity informative stimuli to a neural network of an implantee is preferably performed using an apparatus or implant having one or more of the features as defined herein.
FIG. 5 is another depiction of plasticity informative stimuli as a function of time as output by the apparatus;
FIG. 6 is another depiction of plasticity informative stimuli as a function of time as output by the apparatus;
(b) representing the cochlear nucleus
(c) representing the superior olive
In the depicted embodiment, the naturally occurring agent that is produced and/or released is one or more neurotrophic factors or neurotrophins, such as Brain Derived Neurotrophic Factor (BDNF). In another embodiment, the neurotrophic factors can be selected from the group comprising NGF, NT-3, NT4/5, NT-6, LIF, GDNF, CNTF, and IGF-1.
In another embodiment, the said naturally occurring agents can comprise one of more factors, other then neurotrophins which have capacity to activate the neurotrophic receptors, for example adenosine, a neuromodulator.
Neurotrophic factors are a key element in establishment and maintenance of synapses. Neurotrophins secreted by the postsynaptic cell are likely to be highly localised owing to their propensity to bind to the cell surface near the secretion site. Endogenous neurotrophins, secreted in response to synaptic activity, induce the morphological changes that lead to the formation of new synaptic contacts. Synaptic action of neurotrophins consists of two modes. In a resting ‘permissive’ mode, neurotrophins are secreted at a low level through constitutive secretion or regulated secretion triggered by subthreshold and low-frequency synaptic activity. This permissive mode provides trophic regulation of synaptic functions, including the ability to generate long-term potentiation. In the active ‘instructive’ mode, neurotrophic factors are secreted as a higher level of response to intense synaptic activity that results in a transient high-level calcium concentration in the post-synaptic cytoplasm. The secretion of neurotrophins may be supplemented by activity-dependent synthesis and transport of neurotrophins. The high level of neurotrophins then induce the modification of synaptic functions and the formation of new synaptic contacts.
Delivery of the plasticity informative stimuli can also be used to elicit outgrow of spiral ganglion cells towards the stimulating electrodes of the array 20. By decreasing the distance between these cells and the stimulating electrode, a better selectivity and sensitivity of the auditory informative stimuli may be achieved.
2. Pairs of cells connected by synapses, e.g. cochlear nucleus (by e.g. ABI, PABI);
FIGS. 2-2 b depict another totally implantable cochlear implant system 40. The implant 40 is capable of operation, at least for a period of time, without reliance on componentry worn or carried external to the body of the implantee.
The implant 40 is adapted for implantation in a recess formed in the temporal bone adjacent the ear of the implantee that is receiving the implant. The implant 40 can be implanted in a manner similar to how the receiver and stimulator unit 22 depicted in FIG. 1 would be implanted.
The implant 40 is capable of operation whilst the battery 43 is being recharged. In order to isolate the battery from the entire package, a thermal and electrical insulating material is provided between the battery 43 and the surrounding housing 41.
The stimulation processor within the circuitry 44 outputs auditory informative stimuli signals to an electrode array, such as array 20 of FIG. 1.
The array is also preferably adapted to output the plasticity informative stimuli as described herein.
The electrode array can comprise an elongate electrode carrier member having a plurality of electrodes mounted thereon. The carrier member is preferably formed from a suitable biocompatible material. In the embodiment depicted in FIG. 1, the material can be a silicone, such as Silastic MDX 4-4210.
In considering the embodiment depicted in FIGS. 2-2 b, it should be appreciated that the implantable unit could be provide without a microphone 42 and speech processor. In this case, the detection of sound performed by the microphone and speech processing using a desired speech strategy could be performed using an external component such as processor 29 depicted in FIG. 1. In this case, the on-board battery 43 is used to power the circuitry 44 to ensure delivery only of plasticity informative stimuli to the array 20.
The stimulator can continue to deliver plasticity informative stimuli until such time as the system recommences delivery of auditory informative stimuli or the on-board battery 43 is discharged. When being used, the external processor 29, having its own battery can be used to recharge the on-board battery 43 using the transcutaneous inductive coupling.
The plasticity informative stimuli delivered by the depicted system to the cochlea 12 is at a frequency less than 5 kHz and preferably at or about 50 Hz.
The delivery of plasticity informative stimuli also preferably occurs at times when the apparatus is incapable of delivering auditory informative stimuli. For example, the delivery of plasticity informative stimuli can occur when the implantee is asleep and not using the apparatus for the delivery of auditory informative stimuli. As depicted in FIG. 3, no auditory stimulation stimuli (line 51) is being delivered to the cochlea 12 and at this time, regular occurrences of plasticity informative stimuli 53 is being delivered to the cochlea 12.
As depicted in FIG. 4, the pattern of the plasticity informative stimuli can comprise a short period (t1) of relatively high frequency stimulus 53 (active part) followed by a long period (t2) of no activity (inactive part), ie. t1<t2, where t1:t2 is at least about 0.2 or smaller. In this embodiment, t1 can be in the range of about 0.001 to about 100 sec. A total period between two stimulations 53 (t1+t2) is defined as a duty cycle. In this embodiment, the duty cycle is the basic unit of a plasticity informative stimulus.
In another embodiment, if the stimuli are applied to multiple, if not all, stimulating electrodes, in a sequential mode, the active part of the duty cycle for one stimulating electrode occurs when all other electrodes are in the inactive part of the duty cycle, so at any given time only one stimulating electrode is active (as depicted in FIG. 6).
In this way, the effect of direct stimulation is taken into account as well as the stimulation delivered by adjoining stimulating electrodes. The “auditory” probability (Pa) for each particular stimulating electrode to deliver plasticity informative stimuli is then a function of the weight (Wi) of auditory informative stimuli, Pai=f(Wi). The function that relates the weight of auditory informative stimuli and probability of delivering plasticity informative stimulus is complex.
Further, the “plasticity” probability (Pp) for each particular stimulating electrode to deliver plasticity informative stimuli is then a function of the weight (Wpi) of plasticity informative stimuli, Ppi=f(Wpi).
The stimulator within the circuitry 44 or housing 22 preferably comprises a processor that processes a set of instructions stored on the processor in the form of software.
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Clasificación internacional A61N1/00, A61N1/36, A61F11/00
Clasificación cooperativa A61N1/36036, A61N1/36082, A61M2210/0662, A61M2205/05, A61M5/14276, A61N1/00
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Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:PARKER, JOHN;MILOJEVIC, DUSAN;SIGNING DATES FROM 20040419 TO 20040517;REEL/FRAME:015431/0309