Brain stimulation treatment in depression
Inventors
Etkin, Amit • Keller, Corey • Wu, Wei
Assignees
US Department of Veterans Affairs
Publication Number
US-11324963-B2
Publication Date
2022-05-10
Expiration Date
2037-04-26
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Provided herein are, for example, systems and methods of diagnosing and treating depression, in which a transcranial magnetic stimulation (TMS) therapy is administered to a subject in need thereof and measuring a TMS evoked response in the subject, are provided. The systems and methods allow tailoring or optimizing of a treatment protocol for maximal individual benefit, thereby providing an individualized and optimized treatment protocol for psychiatric disorders such as depression.
Core Innovation
The invention provides systems and methods for diagnosing and treating depression by administering transcranial magnetic stimulation (TMS) therapy to a subject in need and measuring a TMS evoked response in the subject. This approach allows tailoring or optimizing a treatment protocol to maximize individual benefit, thereby providing an individualized and optimized treatment protocol for psychiatric disorders such as depression.
The problem being solved addresses the high prevalence of depression, which has unsatisfying success rates even with the best pharmacotherapy and psychotherapy, and limitations of existing treatments including electroshock therapy (ECT). There is minimal understanding of how TMS exerts its antidepressant effects, and a need exists for a neural circuit biomarker to track and predict clinical outcomes. Current treatment consistency and effectiveness are insufficient, creating demand for more effective systems and methods for depression diagnosis and treatment.
Claims Coverage
The patent presents 22 inventive features derived from its independent claims, encompassing methods of treating depression by measuring brain connectivity and administering tailored transcranial magnetic stimulation therapy with adaptive parameters.
Treatment of depression based on measured brain connectivity
A method comprising measuring an electrical brain response reflecting brain connectivity that varies from normal (i.e., brain hyperconnectivity), followed by administering TMS therapy in response to such measurement, where variation positively correlates with depression reduction.
Measurement of dual data sets for treatment adaptation
Obtaining a first data set of brain activity via initial measurement and obtaining a second data set measuring a TMS evoked response to guide treatment protocol determination.
Use of multimodal measurement techniques
Measurement of TMS evoked response via methods including EEG, MEG, fMRI, and NIRS, with EEG performed concurrently or immediately post TMS therapy.
Artifact removal using automated algorithms
Employing automated artifact rejection for data measured via EEG to clean TMS-EEG data during assessment.
Time-specific measurement of evoked response
Measuring TMS evoked response at specific post-stimulation time ranges including 25-50 ms, 30-70 ms, 70-120 ms, and 150-250 ms after TMS pulses.
Frequency-specific oscillation analysis
Assessing evoked responses based on amplitude in frequency bands including theta (5-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), and gamma (30-60 Hz) within the first second after a TMS pulse.
Adaptive treatment parameter determination
Determining treatment protocols by adapting frequency, intensity, duration, waveform, pattern, and site of TMS, including coil site location and angle based on brain activity data.
Selection based on modulation of evoked response
Selecting TMS protocols that provide substantial modulation of the evoked response or cause significant differences between baseline and post-TMS brain activity data sets.
Changing TMS site and coil parameters
Modifying treatment by altering a TMS site or coil position and angle relative to the subject's head to improve effectiveness.
Adjusting TMS frequency and intensity
Increasing or decreasing frequency and intensity parameters of TMS treatment by specified percentages relative to planned or prior parameters.
Modifying treatment duration and patterns
Prolonging or reducing treatment duration and changing waveform or pattern of TMS administration as part of treatment adaptation.
Termination of TMS treatment as adaptation
Allowing for termination of TMS treatment based on measurements and response during therapy.
Use of repetitive, single pulse, or paired pulse TMS modalities
Employing various TMS modalities including repetitive TMS, single pulse TMS, and paired pulse TMS, with paired pulse initial pulses preceding by intervals of about 50 to 250 milliseconds, used to assess intracortical inhibition.
Administering TMS to specific brain regions
Delivering TMS therapy to targeted regions including left or right dorsolateral prefrontal cortex (DLPFC), dorsal cingulate, dorsomedial prefrontal cortex, frontopolar cortex, or ventrolateral prefrontal cortex.
Repeating administering and measuring steps
Performing repeated TMS administrations and measuring evoked responses, either in real-time within hours or following completion of a treatment course, to monitor and adapt therapy.
Use of machine learning for treatment adaptation
Implementing machine learning protocols to analyze TMS-evoked response data and perform real-time or session-based protocol adaptations for individualized treatment.
The claims cover a comprehensive method of treating depression through measuring brain connectivity and TMS evoked responses, with adaptive selection and modification of TMS treatment parameters such as site, frequency, intensity, duration, waveform, pattern, and termination according to individualized patient responses and machine learning-guided adjustments.
Stated Advantages
Provides individualized and optimized treatment protocols for maximal individual benefit in treating psychiatric disorders such as depression.
Enables real-time monitoring and adjustment of TMS therapy based on measured brain responses.
Facilitates prediction and tracking of clinical outcomes through neural biomarkers.
Improves treatment consistency and effectiveness compared to existing methods.
Allows non-invasive assessment and targeted modulation of brain networks related to depression.
Documented Applications
Treatment of major depressive disorder in patients, including those with medication resistance or intolerable antidepressant side effects.
Use of TMS evoked response measurements to tailor and optimize TMS therapeutic protocols for individuals suffering from depression.
Prediction and monitoring of clinical outcome during and after TMS treatment courses for depression.
Closed-loop TMS therapy where treatment parameters are adjusted in real-time based on neural feedback.
Use in clinical settings to improve efficacy and personalize non-invasive brain stimulation therapies for psychiatric disorders.
Interested in licensing this patent?