Neurostimulation system for central nervous stimulation (CNS) and peripheral nervous stimulation (PNS)

Abstract

The present disclosure relates to a neuromodulation and/or neurostimulation system comprising at least the following components: at least one sensing unit, at least control unit, at least one stimulation unit, at least one Central Nervous System (CNS) stimulation module, at least one Peripheral Nervous System (PNS) stimulation module, wherein at least one of the components of the neuromodulation and/or neurostimulation system is implantable.

Claims

1. A neuromodulation and/or neurostimulation system comprising at least the following components: at least one sensing unit, at least one control unit, at least one stimulation unit that comprises at least one Implantable Pulse Generator (IPG), at least one Central Nervous System (CNS) stimulation module comprising electrodes for providing CNS stimulation configured to evoke at least one of a gait pattern, grasp type, or movement, at least one Peripheral Nervous System (PNS) stimulation module comprising electrodes for providing PNS stimulation configured to refine the evoked at least one of the gait pattern, grasp type, or movement; and wherein the IPG is at least one of the components of the neuromodulation and/or neurostimulation system that is implantable; wherein the at least one control unit is configured to: during a treatment, provide the CNS stimulation via the CNS stimulation module, and provide the PNS stimulation with different stimulation frequencies, wherein the PNS stimulation directly stimulates muscles via the PNS stimulation module.

2. The system according to claim 1, wherein the CNS stimulation module is or comprises an epidural stimulation module capable to provide epidural spinal stimulation.

3. The system according to claim 1, wherein the PNS stimulation module is a Functional Electrical Stimulation (FES) module capable to provide electrical stimulation of peripheral nerves.

4. The system according to claim 1, wherein the components of the neuromodulation and/or neurostimulation system form a closed-loop system.

5. The system according to claim 1, wherein the components of the neuromodulation and/or neurostimulation system form an open-loop system.

6. The system according to claim 1, wherein the control unit is configured such that control is done in real-time.

7. The system according to claim 1, wherein at least one electrode of the electrodes for the PNS module has at least one fixation element for anchoring the at least one electrode in or to surrounding structures.

8. The system according to claim 1, wherein the control unit is configured such that based on sensing signals provided and gained by means of the sensing unit, the PNS stimulation provided by the PNS stimulation module and/or the CNS stimulation provided by CNS stimulation module can be adjusted and/or adapted to: at least partially match stimulation control signals provided by the control unit to control the PNS stimulation module and/or the CNS stimulation module with physiological signals related to a move intention of a subject decoded from its brain and/or nervous system, and/or at least partially match the stimulation control signals provided by the control unit to control the PNS stimulation module and/or the CNS stimulation module with a desired kinematic trajectory, and/or at least partially match the stimulation control signals provided by the control unit to control the PNS stimulation module and/or the CNS stimulation module with desired forces with respect to a surface on which the subject is located or that the subject is touching.

9. The system according to claim 8, wherein the control unit is configured such that the sensing signals provided by the sensing unit can be decoded; wherein the sensing signals are related to movement of the subject; and wherein movement of the subject includes one or more of continuous movement of the subject, signals related to force(s), EMG activity, and/or kinematic trajectories.

10. The system according to claim 1, wherein the control unit is configured such that the PNS stimulation provided by the PNS stimulation module and the CNS stimulation provided by the CNS stimulation module during the treatment is at least partially interleaved.

11. The system according to claim 1, wherein the control unit is configured such that the PNS stimulation provided by the PNS stimulation module and the CNS stimulation provided by the CNS stimulation module during the treatment is at least partially superimposed; and wherein the control unit is configured such that the different frequencies provided during the PNS stimulation is within a frequency range.

12. A method of providing neuromodulation and/or neurostimulation to a patient having a spinal cord injury, comprising: providing Central Nervous System (CNS) stimulation configured to evoke at least one of a gait pattern, grasp type, or movement combined with Peripheral Nervous System (PNS) stimulation configured to refine the evoked at least one of the gait pattern, grasp type, or movement, by using a neuromodulation and/or neurostimulation system, the neuromodulation and/or neurostimulation system comprising at least the following components: at least one sensing unit, at least one control unit, at least one stimulation unit, at least one Central Nervous System (CNS) stimulation module for providing the CNS stimulation, at least one Peripheral Nervous System (PNS) stimulation module for providing the PNS stimulation; wherein at least one of the components of the neuromodulation and/or neurostimulation system is implantable or at least partially implantable; and wherein the PNS stimulation directly stimulates muscles, and wherein providing the CNS stimulation combined with the PNS stimulation includes providing the PNS stimulation at different frequencies.

13. The method of claim 12, wherein the CNS stimulation comprises epidural spinal stimulation below a level of the spinal cord injury.

14. The method of claim 12, wherein the control unit is configured such that based on sensing signals provided and gained by means of the sensing unit, the PNS stimulation provided by the PNS stimulation module and/or the CNS stimulation provided by CNS stimulation module can be adjusted and/or adapted to: at least partially match stimulation control signals provided by the control unit to control the PNS stimulation module and/or the CNS stimulation module with physiological signals related to a move intention of a subject decoded from its brain and/or nervous system, and/or at least partially match the stimulation control signals provided by the control unit to control the PNS stimulation module and/or the CNS stimulation module with a desired kinematic trajectory, and/or at least partially match the stimulation control signals provided by the control unit to control the PNS stimulation module and/or the CNS stimulation module with desired forces with respect to a surface on which the subject is located or that the subject is touching; and wherein the control unit is configured such that the sensing signals provided by the sensing unit can be decoded, the sensing signals related to movement of the subject, and wherein movement of the subject includes one or more of continuous movement of the subject, signals related to force(s), EMG activity, and/or kinematic trajectories.

15. The method of claim 12, wherein the control unit is configured such that the PNS stimulation provided by the PNS stimulation module and the CNS stimulation provided by the CNS stimulation module is at least partially interleaved or at least partially superimposed; and wherein the different frequencies are within a frequency range.

16. The method of claim 12, wherein the CNS stimulation activates afferent sensory neurons entering the spinal cord of the patient.

17. The method of claim 12, wherein the control unit is capable to independently control and switch on and off either the PNS stimulation module or the CNS stimulation module.

18. The method of claim 12, wherein the CNS stimulation does not directly stimulate motor-neurons.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Further details and advantages of the present disclosure shall now be disclosed in connection with the drawings.

(2) FIG. 1 shows a schematic view of the layout of an embodiment according to the present disclosure of the neuromodulation and/or neurostimulation system.

(3) FIG. 2 shows a schematic view of the implanted system and the subject being equipped with the system.

(4) FIG. 3 shows a schematic overview about a feasibility study conducted with rats, showing an example of the system that targets lower limb movements according to the present disclosure.

(5) FIG. 4 shows a further schematic overview about a feasibility study conducted with rats, showing an example of how CNS and PNS stimulation may be used based on recorded sensing signals in the framework of restoring lower limb movement for the system and method according to the present disclosure.

(6) FIG. 5 shows a further schematic overview about a feasibility study conducted with rats, providing a proof of concept for the system and method according to the present disclosure.

(7) FIG. 6 shows a further illustration of gait patterns produced by CNS stimulation under the form of EES only and of gait patterns produced by a combined PNS and CNS stimulation, with PNS locally refining the produced patterns depending on the frequency of PNS stimulation that is employed, providing an illustration of the efficiency of the system for restoring refined lower limb movements according to the present disclosure.

(8) FIG. 7 shows a flow chart showing an example of how the embodiment according to the present disclosure of the neuromodulation and/or neurostimulation system is operated.

DETAILED DESCRIPTION OF DRAWINGS

(9) FIG. 1 shows in a schematical view the layout of the neuromodulation and/or neurostimulation system 10 according to the present disclosure.

(10) The system 10 comprises the components sensing unit 12, control unit 14, stimulation unit 16, Central Nervous System (CNS) stimulation module 18 and a Peripheral Nervous System (PNS) stimulation module 20.

(11) The stimulation unit 16 comprises one Implantable Pulse Generator (IPG) 22 for the CNS stimulation module 18 and another IPG 24 for the PNS stimulation module 20.

(12) It is also possible that only one IPG for both the CNS stimulation module 18 and for the PNS stimulation module 20 is provided.

(13) The system 10 is at least partially implantable, but also comprises sensors, which are or are not implanted and connected either via wires to a connector and then to a recording chamber, or with a wireless data transmission link with the control unit 14 (see FIG. 2).

(14) As can be seen in FIG. 2, there are sensing units 12a and 12b, which are implanted in the patient. These sensing units 12a, 12b are sensors to monitor and sense physiological signals, here sensing electrodes.

(15) The control unit 14 is also implanted in the patient P. It is also possible that this control unit is not implanted.

(16) The control unit 14 comprises at least one memory M.

(17) This memory provides storage capacity for data, inter alia control instructions for performing the control of the system 10.

(18) Such instructions include but are not limited to how to match stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with physiological signals related to a move intention of a subject decoded from its brain and/or nervous system, and/or to match the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with a desired kinematic trajectory, and/or to match the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with desired forces with respect to a surface, on which the subject is located or that the subject is touching, and/or to match the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with muscle activation for certain gait patterns and/or grasp types and/or movements.

(19) These instructions may be part of a control routine or control software or stored as separate software modules or stored into the memory as instruction data.

(20) The link between sensor signals and the instructions may be realized by providing respective meta data, which are stored separately in the memory M, for example in a meta data memory part or storage.

(21) The CNS stimulation module 18 and the PNS stimulation module 20 may also be implanted in the patient P.

(22) Thus, also the respective IPGs 22 and 24 may be implanted in the patient P.

(23) However, there may also be sensors 12c and 12d, which may not be implanted, but which may be attached to the skin of the patient P and provided as wearables. They may be attached to the skin of the patient P by gluing or worn as gloves (e.g. 12c) or the like.

(24) The Central Nervous System stimulation module 18 is in the shown embodiment an epidural stimulation module capable to provide epidural stimulation via electrodes 25.

(25) Generally, it may be also provided as a stimulation module that is capable to provide subdural stimulation or intra-cortical stimulation or intra-spinal stimulation.

(26) The PNS stimulation module 20 may be a functional electrical stimulation module capable to provide electrical stimulation of the peripheral nerves (e.g. PNS stimulation) via electrodes 26.

(27) As can be seen in FIG. 1 and FIG. 2, the PNS stimulation module 20 comprises electrodes 26.

(28) The electrodes 26 may be implanted and may have fixation elements for anchoring the electrodes 26 in the surrounding structures at the implantation side.

(29) The control unit 14 may receive signals from the various sensors of FIG. 1 and FIG. 2 and may employ the various actuators of FIG. 1 and FIG. 2 to adjust stimulation parameters based on the received signals and instructions stored on the memory of the control unit 14.

(30) The control unit 14 may be configured such that based on the sensing signals provided and gained by means of the sensing unit 12, the stimulation provided by the PNS stimulation module 20 and/or provided by CNS stimulation module 18 may be adjusted and/or adapted to match the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with physiological signals related to a move intention of a subject decoded from its brain and/or nervous system, and match the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with a desired kinematic trajectory, and match the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with desired forces with respect to a surface, on which the subject is located or that the subject is touching, and match the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with muscle activation for certain gait patterns and/or grasp types and/or movements.

(31) Furthermore, the control unit 14 may be configured such that signals provided by the sensing unit 12 and related to movement of the subject may be decoded, for example continuous movement of the subject and/or signals related to force(s) and/or EMG activity and/or kinematic trajectories may be decoded.

(32) The system 10 may work as a closed-loop system in real-time.

(33) In particular, the stimulation signals provided by the CNS stimulation module 18 and its electrodes 25 and by PNS stimulation module 20 and its electrodes 26 may be monitored and recorded together with the respective response of the patient by means of the sensing unit(s) and sensor(s) 12, 12a, 12b, 12c, 12d.

(34) It is also possible in general that the system 10 is and may work as a open-loop system. In particular, it is possible that there might be pre-programmed sequences of stimulation sets or patterns to achieve a desired motor outcome.

(35) In particular, the sensing signals may be used to influence the stimulation signals and the stimulation signals and the physiological response thereto is again sensed by the sensing unit 12 and again influences the control unit 14.

(36) This way of working may be controlled by the control unit 14, which may be configured such that the control is done in real-time.

(37) Real-time controlling and working of the system 10 means that the control is done with minimum delay, i.e. within a range of approx. 0 up to 30 ms.

(38) The control unit 14 may be configured such that the PNS stimulation provided PNS stimulation module 20 and the CNS stimulation provided by the CNS stimulation module 18 is at least partially interleaved.

(39) Also, the control unit 14 may be configured such that the PNS stimulation provided by the PNS stimulation module 20 and the CNS stimulation provided by CNS stimulation module 18 is at least partially superimposed.

(40) By interleaving or superimposing the signals, it may be possible to stimulate in a tailor-made way.

(41) Moreover, the control unit 14 may be configured such that the stimulation provided by either the PNS stimulation module 20 or the CNS stimulation module 18 is at least partially used for correction of the stimulation effect provided by the other stimulation module to refine motor output.

(42) Furthermore, the control unit 14 may be capable to independently control and switch on and off either the PNS stimulation module 20 or the CNS stimulation module 18. In other words, the PNS stimulation module 20 and the CNS stimulation module 18 may be controlled independently from each other.

(43) Such a control may be done by the control unit 14.

(44) The function of the system 10 can be described as follows:

(45) The system 10 provides a new electrical stimulation paradigm for the restoration or fine and controllable motor function that targets both the central and the peripheral nervous system in a refined neuroprosthetic system addressing neuromotor disorders. As described above, in combining electrical stimulation of the central nervous system (spinal cord) with intermittent electrical stimulation of the peripheral nerves in real-time instead of using either spinal cord stimulation or nerve stimulation alone, a specific and more general stimulation approach may be established.

(46) It may be possible to exploit the complementary advantages of both stimulation types.

(47) In unimpaired individuals, motor outputs are constantly refined and adjusted based on information from the periphery (for instance, proprioception, sensation, vision).

(48) To achieve such a fine-tuning, stimulation paradigms may need to recruit specific muscles selectively to compensate for imprecisions in the motor output generated by central stimulation paradigms.

(49) The system 10 may be able to use information from the peripheries and from the Central Nervous System in order to refine and adjust the desired stimulation output either by way of the CNS stimulation module 18 or the PNS stimulation module 20.

(50) Thus, there may be a combination of electrical stimulation of the spinal cord and the peripheral nerves. The combination of both strategies may yield a highly refined and much more efficient neuroprosthetic rehabilitation of motor control, with potential applications in both the upper and lower limb paralysis framework.

(51) In the framework of paralysis, spinal cord stimulation recruits functional networks below the lesion and activates muscle synergies that act as building blocks for functional movements. While the created movement may be strong as a result of the activation of the movement related muscle synergies, control and execution of fine movements may be a difficult task as the generated movement and its imprecisions may hinder fluidity and full functionality in the potential space of the movement.

(52) Peripheral nerve stimulation may target directly specific muscles and may produce selective and controllable activations that may allow expanding the reachable space of movements. The bottleneck of this extreme selectivity that arises from the direct projections from the nerve to the muscle it innervates consists in the impossibility of generating functional and weight-bearing movements. In fact, functional and multi-joint movements require the recruitment of muscles that are innervated by more than one nerve, and stimulating one nerve may not suffice to generate a usable movement.

(53) As such, the combination of both stimulation types may leverage the advantages of each stimulation paradigm and may restore functional, complex and fine movements after paralysis.

(54) As shown in FIG. 3, FIG. 4, FIG. 5, and FIG. 6, the feasibility of the above paradigm has been demonstrated in a rat model of paralyzing spinal cord injury.

(55) FIG. 3 shows in a schematic view an example of an implementation of the system 10′ in a feasibility study conducted with a rat 100 that aims at restoring refined locomotion after paralyzing spinal cord injury.

(56) Similar implementation is possible in other mammals or human beings.

(57) There is a CNS stimulation module 18′ and a PNS stimulation module 20′ having the structural and functional features as described above, but adjusted to the size of the rat 100.

(58) In this example, the spinal cord 102 of the rat 100 is injured at the mid-thoracic level (approx. T8/T9) by either a severe spinal cord contusion or a complete spinal cord transection (cf. lower left part of FIG. 3).

(59) EMG signals from ankle muscles 104 are recorded via bipolar wire electrodes 106 of a neural polyimide-based multi-channel implant 107 implanted within the muscles (cf. lower right and upper left part of FIG. 3).

(60) Leg joint kinematics are recorded by means of a recording system 101 via reflective markers that are glued with double-sided tape to the joints. CNS stimulation is provided on the epidural lumbosacral spinal cord 102 via two monopolar wire electrodes 108, 110 placed on levels L2 and S1 respectively (cf. upper right part of FIG. 3).

(61) 5HT7, 5HT2 and 5HT1a represent pharmaceuticals that may be used to support the stimulation.

(62) The recorded signals relate to kinematics (i.e. stance, swing and drag) of parts of lower extremity, here the crest, i.e. kinematic crest signal K1, the hip, i.e. kinematic hip signal K2, the knee, i.e. kinematic knee signal K3, the ankle, i.e. kinematic ankle signal K4, and the foot, i.e. kinematic foot signal K5.

(63) Furthermore, by means of the recording system 101 the EMG activity is recorded. Here the EMG signals related to ankle, flexor and extensor are recorded.

(64) The signals recorded by means of the recording system 101 may be stored in a memory of the recording system 101. They may also be used by the control unit of the system 10′ (not shown, but functionality is described above in connection with control unit 14).

(65) PNS stimulation is provided via an intra-neural polyimide-based multi-channel implant that is inserted in the proximal sciatic nerve 112 (above the branching point into separate fascicles) (cf. lower right part of FIG. 3).

(66) In this setup, the wires from the EMG electrodes and the epidural spinal cord electrodes are all routed subcutaneously to a common connector that is cemented with dental cement to the skull of the rat. The amplifier for EMG signals and stimulator providing the spinal cord may be plugged to this connector. The wires from the intra-neural electrode are routed subcutaneously to a plug on the lower back of the rat, to which the stimulator may be plugged.

(67) As shown in the upper left part of FIG. 3, the kinematics (of crest, hip, knee, ankle and foot) and the respective EMG activity (for ankle, flexor and extensor) are recorded by the sensors of the system 10′.

(68) FIG. 4 shows an example of how such a system 10′ as presented in FIG. 3 may be used in real time to generate functional and refined movements.

(69) Epidural electrodes, i.e. the two monopolar wire electrodes 108, 110 (cf. upper right part of FIG. 3 and CNS stimulation module 18′) on the lumbosacral spinal cord 102 electrically stimulate the locomotor networks and produce functional gait patterns.

(70) The produced movements of the rat 100 on a treadmill 114 are monitored in real time using reflective markers that are glued on the hind-limb joints (crest, hip, knee, ankle, foot-tip) inter alia by means of a camera 116.

(71) In this example the control unit 14′ (which can inter alia control wirelessly the components of the system 10′) compares the produced gait patterns in real-time to a model gait cycle and recognizes main events and their timing such as foot strike, toe-off or maximal foot height in real time.

(72) Also in this example, if the produced gait would not match the desired model gait cycle, selective PNS is used at defined phases during the gait cycle to refine the produced gait.

(73) Bilateral intraneural electrodes in the right and left sciatic nerve deliver phasic electrical stimulation to correct for the noticed imprecisions in the patterns and refine the gait.

(74) In this example, the intensity of the PNS is controlled with the frequency of the delivered pulses.

(75) FIG. 5 (top) shows preliminary results that were obtained using the system described in FIGS. 3 and 4. Ankle flexion was enhanced through selective sciatic nerve stimulation of the peroneal fascicle at the beginning of the swing phase while ankle extension was enhanced through selective stimulation of the sciatic nerve tibial branch via different active sites at the end of stance phase.

(76) Adding PNS to CNS had major effects on the leg being stimulated and on the contralateral leg. In fact, a significant increase was obtained in the step height of the leg that was additionally stimulated with PNS.

(77) Additionally, the dragging of the foot that was stimulated additionally with PNS was significantly reduced when compared to CNS only.

(78) Adding PNS by means of the Peripheral Nervous System (PNS) stimulation module 20 on one leg also had a significant effect on the other leg, for instance it increased the stride length of that leg considerably.

(79) This refinement of the gait allowed the rats 100 to walk overground (FIG. 5 bottom) and climb on stairs (see middle section of FIG. 5 with stairs ST) with significantly reduced amount of failures and tumbling.

(80) This present disclosure has enormous potential to restore fine movements in people affected by paralysis.

(81) Especially in the case of upper limb paralysis, spinal cord stimulation has shown fairly limited success in being able to selectively activate forearm or finger muscles.

(82) Activating the reaching and grasping synergies centrally and refining those peripherally has thus enormous potential for the restoration of functional, refined and controllable upper limb movements after paralysis.

(83) Central neuromodulation, under the form of electrical stimulation of the spinal cord produces motor synergies resulting in functional movements but those movements are restricted in space. Stimulating the peripheral nerves additionally with different stimulation frequencies on top of the central neuromodulation allows i) to gradually refine the produced movements and ii) to locally expand the reachable space in a highly controllable way.

(84) FIG. 6 illustrates this concept in the framework of lower limb paralysis.

(85) Foot trajectories T1, T1′ (black) are obtained via central neuromodulation (electrical epidural stimulation of the lumbo-sacral spinal cord) and exhibit moderate step heights and foot dragging. Superimposition of selective sciatic nerve stimulation allows to further gradually modulate the gait cycle and enhance the movement, for instance through increasing the step height of the stimulated leg (trajectories T2, at 30 Hz, and trajectories T3, at 70 Hz) with increased frequency, or reducing the foot dragging contralateral (trajectories T2′, at 30 Hz, and trajectories T3′, at 70 Hz). Peripheral nerve stimulation with graded frequencies gradually enhances the general stepping pattern of both the stimulated and the contralateral foot and allows thus, in combination with central neuromodulation, to improve controlled movement restoration.

(86) The lower part of FIG. 6 relates to enhanced ipsilateral flexion and the foot trajectories are shown for EES stimulation only as trajectories T1 and also superimposed to that the trajectories T3 of PNS in addition to the EES stimulation.

(87) The PNS stimulation is done in a range between 30 Hz (trajectories T2) to 70 Hz (trajectories T3).

(88) The upper part of FIG. 6 relates to enhanced contralateral extension and the foot trajectories are shown for EES stimulation only as trajectories T1′ also superimposed to that the trajectories T3′ of PNS in addition to the EES stimulation.

(89) The PNS stimulation is done in a range between 30 Hz (trajectories T2′) to 70 Hz (trajectories T3′).

(90) FIG. 7 relates to a flow chart showing an example how the closed-loop embodiment according to the present disclosure of the neuromodulation and/or neurostimulation system 10 is operated.

(91) In step S1 physiological signals of the patient (or as shown in the example of FIG. 3-6 of a mammal, here a rat) are gained and recorded. This is done by the sensing unit 12.

(92) In step S2 the gained signals are provided to the control unit 14.

(93) In step S3 an initial stimulation parameter set is provided by the control unit 14.

(94) In step S4 a matching of the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with physiological signals related to a move intention of a subject decoded from its brain and/or nervous system is performed.

(95) In step S5 a matching of the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with a desired kinematic trajectory is performed.

(96) In step S6 a matching of the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with desired forces with respect to a surface, on which the subject is located or that the subject is touching is performed.

(97) In step S7 a matching of the stimulation control signals provided by the control unit 14 to control the PNS stimulation module 20 and/or the CNS stimulation module 18 with muscle activation for certain gait patterns and/or grasp types and/or movements is performed.

(98) Steps S4 to S7 can be performed sequentially or in parallel.

(99) In step S8 a decoding of physiological signals is performed. This is done by the control unit 14, which is configured such that signals provided by the sensing unit 12 and related to movement of the subject can be decoded, especially continuously movement of the subject and/or signals related to force(s) and/or EMG activity and/or kinematic trajectories can be decoded.

(100) As can be seen from the flow chart, the system 10 works as a closed-loop system in real-time.

(101) After step S8 it is continued with step S1.

(102) Note that the example control and estimation routines included herein can be used with various neuromodulation and/or neurostimulation system configurations. The control methods and routines disclosed herein may be stored as executable instructions in non-transitory memory and may be carried out by the control unit in combination with the various sensors, actuators, and other system hardware. The specific routines described herein may represent one or more of any number of processing strategies such as event-driven, interrupt-driven, multi-tasking, multi-threading, and the like. As such, various actions, operations, and/or functions illustrated may be performed in the sequence illustrated, in parallel, or in some cases omitted. Likewise, the order of processing is not necessarily required to achieve the features and advantages of the example embodiments described herein, but is provided for ease of illustration and description. One or more of the illustrated actions, operations and/or functions may be repeatedly performed depending on the particular strategy being used. Further, the described actions, operations and/or functions may graphically represent code to be programmed into non-transitory memory of the computer readable storage medium in the control unit, where the described actions are carried out by executing the instructions in a system including the various hardware components in combination with the electronic control unit.

REFERENCES

(103) 10 Neuromodulation and/or neuro stimulation system 12 ensing unit 12a Sensing unit 12b Sensing unit 12c Sensor 12d Sensor 14 Control unit 16 Stimulation unit 18 Central Nervous System (CNS) stimulation module 20 Peripheral Nervous System (PNS) stimulation module 22 Implantable Pulse Generator (IPG) 24 Implantable Pulse Generator (IPG) 25 Electrodes 26 Electrodes 10′ System 14′ Control Unit 18′ Central Nervous System (CNS) stimulation module 20′ Peripheral Nervous System (PNS) stimulation module 100 Rat 102 Spinal Cord (Rat) 104 Ankle Muscle 106 Bipolar Wire Electrode 107 Neural Polyimide-Based Multi-Channel Implant 108 Monopolar Wire Electrode 110 Monopolar Wire Electrode 112 Sciatic Nerve 114 Treadmill 116 Camera P Patient K1 Kinematic Crest Signal K2 Kinematic Hip Signal K3 Kinematic Knee Signal K4 Kinematic Ankle Signal K5 Kinematic Foot Signal M Memory ST stairs S1 Method Step S1 S2 Method Step S2 S3 Method Step S3 S4 Method Step S4 S5 Method Step S5 S6 Method Step S6 S7 Method Step S7 S8 Method Step S8 T1 trajectory (EES only) T2 trajectory T3 trajectory T1′ trajectory (EES only) T2′ trajectory (EES and PNS with Hz) T3′ trajectory