Granted Patent B2

US 12,409,325 · App. 17/667,009 · Granted Sep 9, 2025

Inventors: Saman Hagh Gooie (Hamburg, DE); Bálint Várkuti (Munich, DE); Ricardo Smits Serena (Munich, DE)

Assignee: Ceregate GmbH

A61N1/36171A61N1/36135A61N1/36178A61N1/37247

Abstract

Claims (74)

1. A closed-loop calibration method for updating a current set of stimulation parameters of a device, the method comprising, by a processor:

applying, via a neurostimulation interface device operably connected to the device, a burst sequence of stimulation pulses to a plurality of afferent sensory neurons targeting a sensory cortex area involved with decoding information transmitted by the device, wherein the sequence of stimulation pulses is associated with the current set of stimulation parameters, and wherein the sequence of stimulation pulses is configured to elicit a bioelectric response in the plurality of afferent sensory neurons;

recording, via the neurostimulation interface device, the elicited bioelectric response of the stimulated afferent sensory neurons;

deriving, based at least in part on the recorded bioelectric response, a neural excitability profile characterizing a non-linear, dynamic excitation behavior of the plurality of afferent sensory neurons corresponding to the applied sequence of stimulation pulses; and

adjusting, based on the derived excitability profile, at least one stimulation parameter of the current set of stimulation parameters to obtain an updated set of stimulation parameters.

2. The method of claim 1 ,

wherein the burst sequence of stimulation pulses is part of a neurostimulation signal or signal sequence applied by the device to elicit an artificial sensory perception in a sensory cortex area receiving input signals from at least a subset of the plurality of afferent sensory neurons,

wherein the burst sequence of stimulation pulses comprises a burst sequence of essentially identical pulses and/or phasic stimulation pulses; and

wherein an intra-burst pulse frequency is at least 50 Hz.

3. The method of claim 1 ,

wherein recording the elicited bioelectric response comprises recording the bioelectric response while the burst sequence of stimulation pulses is being applied, and

wherein deriving the excitability profile is based at least in part on analyzing intra-burst variations of the recorded bioelectric response.

4. The method of claim 3 ,

wherein bioelectric response is recorded after each stimulation pulse or continuously during the sequence.

5. The method of claim 1 , wherein a sampling rate of the recording is equal or larger than an inverse of a time duration between two stimulation pulses of the burst sequence of stimulation pulses.

6. The method of claim 1 ,

wherein at least two consecutive burst sequences are applied, and

wherein deriving the excitability profile is based at least in part on analyzing inter-burst variations of the recorded bioelectric response.

7. The method of claim 6 ,

wherein one or more stimulation parameters including a pulse frequency are varied among the at least two consecutive burst sequences.

8. The method of claim 1 ,

wherein at least two burst sequences are applied,

wherein deriving the excitability profile comprises analyzing the bioelectric response corresponding to each stimulation pulse within each burst sequence, and

wherein deriving the excitability profile comprises analyzing variations among the recorded bioelectric responses within one burst sequence or among consecutive burst sequences.

9. The method of claim 1 ,

wherein deriving the excitation profile comprises extracting temporal variations or dynamics of recording signal parameters or derived metrics from a plurality of subsequent recordings of the elicited bioelectric response, and

wherein the method further comprises, by the processor:

classifying the excitation behavior of a subset of the stimulated afferent sensory neurons using a closed set of discrete categories and based at least in part on the derived excitability profile.

10. The method of claim 9 ,

wherein classification is based at least in part on analyzing a temporal variation or dynamic of the excitability profile within one burst sequence of stimulation pulses or among consecutive burst sequences of stimulation pulses.

11. The method of claim 1 ,

wherein deriving the excitability profile is based at least in part on correlating the recorded bioelectric response with predictions of a non-linear mathematical model of neuronal excitability,

wherein the non-linear mathematical model comprises model parameters that vary slowly in time to capture physiologic adaptation mechanisms of the stimulated afferent sensory neurons.

12. The method of claim 1 ,

wherein the elicited bioelectric response comprises one or more compound action potentials (CAPs), and

wherein deriving the excitability profile comprises determining one or more of:

a difference of a second peak and a first valley within the elicited bioelectric response,

a number of detectable peaks or troughs,

a measure of synchrony among the bioelectric responses recorded for the burst sequence or among subsequent burst sequences of stimulation pulses, and

a delay between a stimulation pulse and the corresponding CAP.

13. The method of claim 1 ,

wherein adjusting the at least one stimulation parameter comprises comparing the derived excitability profile with a reference excitability profile,

wherein the reference excitability profile includes one or more of the following:

an amplitude of a reference bioelectric response,

intra-burst variations among bioelectric responses corresponding to single stimulation pulses within a burst sequence, and

intra-burst variations of the bioelectric response corresponding to the first and the last stimulation pulse within a burst stimulation sequence.

14. The method of claim 13 ,

wherein the reference excitability profile corresponds to a specific artificial sensory perception corresponding to a set of reference stimulation parameters associated with the reference excitability profile.

15. The method of claim 1 , the method further comprising, by the processor:

applying, via the neurostimulation interface device, a neurostimulation signal or signal sequence to at least a subset of the afferent sensory neurons using the updated stimulation parameters

wherein the neurostimulation signal or signal sequence is configured to elicit an artificial sensory perception in a sensory cortex area receiving afferent sensory input from the stimulated subset of afferent sensory neurons.

16. The method of claim 1 ,

wherein the device comprises a neurostimulation (NS) device or a computer-brain interface (CBI) device.

17. A non-transitory computer-readable memory medium storing program instructions which, when executed by a processor, cause a device to:

apply, via a neurostimulation interface device operably connected to the device, a burst sequence of stimulation pulses to a plurality of afferent sensory neurons of an individual targeting a sensory cortex area involved with decoding information transmitted by the device, wherein the sequence of stimulation pulses is associated with the current set of stimulation parameters, and wherein the sequence of stimulation pulses is configured to elicit a bioelectric response in the plurality of afferent sensory neurons;

record, via the neurostimulation interface device, the elicited bioelectric response of the stimulated afferent sensory neurons;

derive, based at least in part on the recorded bioelectric response, a neural excitability profile characterizing a non-linear, dynamic excitation behavior of the plurality of afferent sensory neurons corresponding to the applied sequence of stimulation pulses; and

adjust, based on the derived excitability profile, at least one stimulation parameter of the current set of stimulation parameters to obtain an updated set of stimulation parameters.

18. The non-transitory computer-readable memory medium of claim 17 ,

wherein the burst sequence of stimulation pulses is part of a neurostimulation signal or signal sequence applied by the device to elicit an artificial sensory perception in a sensory cortex area receiving input signals from at least a subset of the plurality of afferent sensory neurons,

wherein the burst sequence of stimulation pulses comprises a burst sequence of essentially identical pulses and/or phasic stimulation pulses; and

wherein an intra-burst pulse frequency is at least 50 Hz.

19. A device, comprising:

a processor;

a non-transitory computer-readable memory medium operably coupled to the processor; and

a neurostimulation interface device operably coupled to the processor, wherein the device is configured to:

apply, via the neurostimulation interface device, a burst sequence of stimulation pulses to a plurality of afferent sensory neurons of an individual targeting a sensory cortex area involved with decoding information transmitted by the device, wherein the sequence of stimulation pulses is associated with the current set of stimulation parameters, and wherein the sequence of stimulation pulses is configured to elicit a bioelectric response in the plurality of afferent sensory neurons;

record, via the neurostimulation interface device, the elicited bioelectric response of the stimulated afferent sensory neurons;

derive, based at least in part on the recorded bioelectric response, a neural excitability profile characterizing a non-linear, dynamic excitation behavior of the plurality of afferent sensory neurons corresponding to the applied sequence of stimulation pulses; and

adjust, based on the derived excitability profile, at least one stimulation parameter of the current set of stimulation parameters to obtain an updated set of stimulation parameters.

20. The device of claim 19 ,

wherein the device comprises:

a neurostimulation (NS) device; or

a computer brain interface (CBI) device.

Assignments (2)

Priority Claims (1)

Continuity (2)

References Cited (76)