# US 11,298,070 B2 · Systems and methods for monitoring neural activity > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,298,070 B2 - Document ID: US11298070B2 - Status: Granted - Kind: B2 - Application number: 16/616,017 - Filed: 2018-05-21 - Published: 2020-05-07 - Granted: 2022-04-12 - Earliest claimed: 2017-05-22 - Assignees: Deep Brain Stimulation Technologies Pty Ltd - Applicants: Deep Brain Stimultation Technologies Pty. Ltd. - Inventors: Nicholas Sinclair; Hugh McDermott; James Fallon; Thushara Perera; Arthur Wesley Thevathasan; Kristian Bulluss - Web page: https://patentgrep.com/patent/US11298070B2 ## CPC - A61B 5/4836: {Diagnosis combined with treatment in closed-loop systems or methods (A61B5/0036 takes precedence)} - A61B 5/377: using evoked responses - A61N 1/0534: {Electrodes for deep brain stimulation} - A61N 1/36067: {Movement disorders, e.g. tremor or Parkinson disease (stimulating motor muscle A61N1/36003)} - A61N 1/36082: {Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease} - A61N 1/36139: {with automatic adjustment} - A61N 1/36146: {specified by the stimulation parameters} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) ## Abstract A method for monitoring neural activity responsive to a stimulus in a brain, the method comprising: a. applying a first stimulus to one or more of at least one electrode implanted in the brain, the first stimulus comprising a first plurality of bursts of stimulation, b. detecting high frequency oscillations (HFOs) between about 200 Hz and about 500 Hz due to neuronal activity at one or more of the at least one electrode implanted in the brain at least partially during application of the first stimulus; c. determining one or more waveform characteristics of the HFOs; and d. generating a second stimulus comprising a second plurality of bursts of stimulation, wherein one or more waveform characteristics of the second stimulus is dependent on the one of more waveform characteristics of the HFOs; and e. applying the second stimulus to one or more of the at least one electrode implanted in the brain. ## Claims ### Claim 1 A method for monitoring neural activity responsive to a stimulus in a brain, the method comprising: a. applying a first stimulus to one or more of at least one electrode implanted in the brain, the first stimulus comprising a first plurality of bursts of stimulation, b. detecting high frequency oscillations (HFOs) between about 200 Hz and about 500 Hz due to neuronal activity at one or more of the at least one electrode implanted in the brain at least partially during application of the first stimulus; c. determining one or more waveform characteristics of the HFOs; and d. generating a second stimulus comprising a second plurality of bursts of stimulation, wherein one or more waveform characteristics of the second stimulus is dependent on the one of more waveform characteristics of the HFOs; and e. applying the second stimulus to one or more of the at least one electrode implanted in the brain. ### Claim 2 (depends on 1) The method of claim 1, wherein the first plurality of bursts comprises a first burst applied for a first time period and having a first waveform characteristic and at least a second burst applied for a second time period following the first time period and having a second waveform characteristic. ### Claim 3 (depends on 2) The method of claim 2, wherein detecting HFOs due to neuronal activity at one or more of the at least one electrode implanted in the brain further comprises: detecting a first high frequency oscillation (HFO) during the first time period and at least a second HFO during the second time period at one or more of the at least one electrode implanted in the brain. ### Claim 4 (depends on 1) The method of claim 1, wherein the one or more waveform characteristics of the HFOs comprises one or more of the following: a) a frequency; b) an amplitude; c) a rate of change of frequency; d) a rate of change of amplitude; and e) a bandwidth. ### Claim 5 (depends on 1) The method of claim 1, wherein the first plurality of bursts and/or the second plurality of bursts are separated by a first pattern time period, each burst comprising a plurality of pulses separated by a second pattern time period, wherein the first pattern time period is greater than the second pattern time period. ### Claim 6 (depends on 5) The method of claim 5, wherein two or more of pulses within at least one of the first plurality of bursts have different amplitudes and/or wherein two or more of pulses within at least one of the second plurality of bursts have different amplitudes. ### Claim 7 (depends on 5) The method of claim 5, wherein the amplitude of a final pulse in each of the first plurality of bursts is substantially identical or wherein the amplitude of a final pulse in each of the second plurality of bursts is substantially identical. ### Claim 8 (depends on 1) The method of claim 1, wherein the one or more waveform characteristics of the second stimulus comprises a frequency, and wherein the frequency is configured to be equal to the frequency of the HFO divided by 1, 2, 3 or 4. ### Claim 9 (depends on 1) The method of claim 1, wherein the one or more waveform characteristics of the HFOs comprises a rate of change of frequency and wherein the one or more characteristics of the second stimulus are configured to maximise the rate of change of the frequency of the HFOs. ### Claim 10 (depends on 1) The method of claim 1, further comprising: determining a correlation between the detected HFOs and a HFO template; and wherein the second stimulus is generated based on the correlation. ### Claim 11 (depends on 1) The method of claim 1, further comprising: whilst applying the second stimulus, simultaneously detecting high frequency oscillations (HFOs) due to neuronal activity at one or more of the at least one electrode implanted in the brain; and determining one or more second waveform characteristics of the detected HFOs during application of the second stimulus. ### Claim 12 (depends on 11) The method of claim 11, further comprising: estimating a degree of progression of a disease associated with the patient based on the one or more first waveform characteristics of the HFOs and the one or more second waveform characteristics of the HFOs; or determining the effect of a therapy provided to the patient based on the one or more first waveform characteristics of the HFOs and the one or more second waveform characteristics of the HFOs. ### Claim 13 (depends on 11) The method of claim 11, further comprising: comparing a common waveform characteristic between the one or more waveform characteristics and the one or more second waveform characteristics. ### Claim 14 (depends on 13) The method of claim 13, wherein the steps of applying the second stimulus whilst simultaneously determining one or more second waveform characteristics of the HFOs are repeated until it is determined that one or more of the at least one electrode is positioned in a target neural structure in the brain. ### Claim 15 (depends on 11) The method of claim 11, further comprising: selecting one or more of the at least one electrode to use for therapeutic stimulation of a target neural structure in the brain based on the one or more waveform characteristics or the one or more second waveform characteristics; and applying a therapeutic stimulus to the target neural structure via the selected one or more of the at least one electrode. ### Claim 16 (depends on 11) The method of claim 11, further comprising: inserting the at least one electrode into the brain along a predefined trajectory; wherein the steps of applying the second stimulus whilst simultaneously determining one or more second waveform characteristics of the HFOs are repeated while the at least one electrode is being inserted to generate a profile of HFO activity with respect to the predefined trajectory and a target neural structure in the brain. ### Claim 17 (depends on 1) The method of claim 1, further comprising: e. detecting a resonant response from the target neural structure evoked by the stimulus at one or more of the at least one electrode in or near a target neural structure of the brain; and f. determining one or more waveform characteristics of the detected resonant response. ### Claim 18 (depends on 1) The method of claim 1, wherein the HFOs have a frequency of between about 230 Hz and about 330 Hz. ### Claim 19 A neuromodulation system, comprising: a lead having at least one electrode adapted for implantation in or near a target neural structure in the brain; a signal generator selectively coupled to one or more of the at least one electrode and configured to: generate and apply a first stimulus to one or more of the at least one electrode, the first stimulus comprising a first plurality of bursts of stimulation; and generate and apply a second stimulus to one or more of the at least one electrode, the second stimulus comprising a second plurality of bursts of stimulation; a measurement device selectively coupled to one or more of the at least one electrode and configured to detect high frequency oscillations (HFOs) between about 200 Hz and about 500 Hz generated from neural activity at one or more of the at least one electrode when implanted in the brain at least partially during application of the first stimulus; and a processing unit coupled to the measurement device and configured to determine one or more waveform characteristics of the detected HFOs, wherein one or more waveform characteristics of the second stimulus is dependent on the one of more waveform characteristics of the HFOs. ### Claim 20 A method for monitoring neural activity responsive to a stimulus in a brain, the method comprising: a. applying a first stimulus to one or more of at least one electrode implanted in the brain, the first stimulus comprising a first plurality of bursts of stimulation, b. detecting high frequency oscillations (HFOs) due to neuronal activity at one or more of the at least one electrode implanted in the brain at least partially during application of the first stimulus; c. determining one or more waveform characteristics of the HFOs; and d. generating a second stimulus comprising a second plurality of bursts of stimulation, wherein one or more waveform characteristics of the second stimulus is dependent on the one of more waveform characteristics of the HFOs; and e. applying the second stimulus to one or more of the at least one electrode implanted in the brain, wherein the first plurality of bursts and/or the second plurality of bursts are separated by a first pattern time period, each burst comprising a plurality of pulses separated by a second pattern time period, wherein the first pattern time period is greater than the second pattern time period.