Brain stimulation treatment in depression
Inventors
Etkin, Amit • Keller, Corey • Wu, Wei
Assignees
US Department of Veterans Affairs
Publication Number
US-12115383-B2
Publication Date
2024-10-15
Expiration Date
2037-04-26
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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. These methods allow for tailoring or optimizing treatment protocols to achieve maximal individual benefit, thereby providing an individualized and optimized treatment for psychiatric disorders such as depression.
The problem being solved is the low success rates in treating depression with existing methods like pharmacotherapy and psychotherapy, with many patients failing to achieve remission and limited options available for treatment-resistant cases. There is a minimal understanding of how TMS exerts antidepressant effects and a need for neural circuit biomarkers to track and predict clinical outcomes.
The disclosed methods involve administering repetitive transcranial magnetic stimulation (rTMS) and measuring the evoked brain response, for example via EEG, MEG, fMRI, or NIRS. By analyzing the subject’s brain activity before and after TMS, the methods facilitate individualized adjustments of treatment parameters such as stimulation site, frequency, intensity, and pattern. The invention also provides automated artifact rejection techniques to enable accurate and real-time analysis of TMS-evoked potentials, enabling closed-loop feedback to optimize treatment efficacy.
Claims Coverage
The patent contains 22 independent claims detailing methods of treating depression using TMS therapy combined with measuring intracortical inhibition and TMS evoked responses, alongside adaptations of treatment protocols based on measured brain activity.
Measuring intracortical inhibition and treating depression by reducing it
The method involves measuring an electrical response of the brain to identify intracortical inhibition in a subject with depression and administering TMS therapy that reduces this intracortical inhibition, thereby treating depression.
Administering TMS to multiple sites and selecting sites based on evoked response
The method includes applying TMS to a plurality of brain sites, measuring the evoked responses at each site, and selecting one or more sites for treatment based on which sites evoke stronger TMS responses.
Measuring TMS evoked response via multiple neurophysiological modalities
TMS evoked response can be measured through electroencephalogram (EEG), magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), or near-infrared spectroscopy (NIRS), concurrently or immediately after TMS therapy.
Using various TMS protocols and parameters for treatment
The TMS therapy can be delivered as repetitive TMS (rTMS), single pulse TMS, or paired pulse TMS, with specified intervals (e.g., 50-250 milliseconds for paired pulses) and frequencies ranging from 1 Hz to 30 Hz or intermittent theta burst stimulation.
Removing artifacts from measured neurophysiological data
The method includes removing one or more artifacts from the data measured via EEG using an automated artifact rejection algorithm to ensure accurate analysis of TMS-evoked responses.
Repeating administration and measurement of TMS therapy responsive to evoked response
The method comprises repeating the administration of TMS therapy and measurement of evoked responses in real-time, responsive to previously measured TMS evoked responses, including within 1-2 hours after initial treatment or following a completed course.
Administering TMS at suprathreshold intensities calibrated to resting motor threshold
The TMS therapy can be delivered at suprathreshold intensity, such as about 120% of the subject's resting motor threshold, to effectively modulate cortical activity.
Correlation of reduction in specific TMS-evoked potentials with clinical improvement
The method observes that greater reduction in p60 and/or p200 TMS-evoked potentials correlates with greater reduction in depressive symptoms, and that larger baseline p200 potentials predict better treatment outcomes.
The claims encompass methods for treating depression by measuring and reducing intracortical inhibition via TMS, selecting stimulation sites based on evoked responses, using various TMS protocols, removing artifacts for clear measurement, and adapting treatment responsively, demonstrating a comprehensive approach to individualized depression therapy.
Stated Advantages
Provides individualized and optimized treatment protocols tailored to the patient's specific brain response for maximal therapeutic benefit.
Enables real-time monitoring and adjustment of TMS parameters based on measured brain activity responses, improving treatment efficacy.
Offers non-invasive and precise approaches to diagnose and track depression treatment outcomes using TMS evoked responses as biomarkers.
Automated artifact rejection improves data quality and reduces processing time, making clinical application more practical.
Predicts clinical outcomes through neural biomarkers such as p200 TMS-evoked potentials and baseline brain connectivity measures.
Documented Applications
Treatment of major depressive disorder using TMS therapy, specifically repetitive TMS targeted to the dorsolateral prefrontal cortex and other prefrontal regions.
Use of TMS evoked response measurements (e.g., via EEG) to individualize and optimize TMS treatment parameters such as stimulation site, frequency, intensity, coil angle, and pattern.
Utilization of closed-loop treatment systems wherein TMS therapy is adjusted in real time based on the subject's TMS evoked brain response.
Stratification of patients based on neural biomarkers to predict and improve clinical outcomes to TMS therapy.
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