Treating Post-Traumatic Stress Disorder

Abstract

1. A method of treating a patient population for post-traumatic stress disorder (PTSD), comprising: selecting a population of patients diagnosed with PTSD; administering NF treatment to said population; and achieving an average reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of 8 to 12 weeks of said administration.

Description

[Technical Field]

[0001] Related Applications This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 63 / 398,248, filed August 16, 2022, the contents of which are incorporated herein by reference in their entirety. [Background technology]

[0002] FIELD AND BACKGROUND OF THE INVENTION The present invention, in some embodiments thereof, relates to the treatment of stress disorders, and more particularly, but not exclusively, to the treatment of post-traumatic stress disorder (PTSD). Summary of the Invention

[0003] Below are some examples of some embodiments of the present invention (an embodiment may include features from more than one example and / or may include fewer than all features of an example).

[0004] Example 1. 1. A method of treating a patient population for post-traumatic stress disorder (PTSD), comprising: Selecting a population of patients diagnosed with PTSD and administering an NF treatment to said population; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of 8 to 12 weeks of said administration; A method comprising:

[0005] Example 2. The method of Example 1, wherein the administering comprises training the selected population with the NF treatment to modulate activation of the amygdala or at least one associated brain region or at least one biomarker thereof.

[0006] Example 3. The method of Example 2, wherein said training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the brain region or at least one biomarker thereof when exposed to at least one interface.

[0007] Example 4. The method of Example 3, wherein the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0008] Example 5. The method according to any one of Examples 1 to 3, wherein the administered NF treatment is functional magnetic resonance imaging (fMRI) neurofeedback treatment.

[0009] Example 6. The method of any one of the preceding examples, wherein said achieving comprises achieving an average reduction of at least a 6 point on the CAPS-5 scale within 3 months of said administration.

[0010] Example 7. The method of any one of the preceding examples, wherein said selecting comprises selecting a population of patients diagnosed with chronic PTSD.

[0011] Example 8. 1. A method of treating a patient population for post-traumatic stress disorder (PTSD), comprising: Selecting a population of patients diagnosed with PTSD and administering NF treatment to said population for a period of 8 to 12 weeks; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of no more than 3 months from said administration; A method comprising:

[0012] Example 9. The method of Example 8, wherein the administering comprises training the selected population with the NF treatment to modulate activation of the amygdala or at least one associated brain region or at least one biomarker thereof.

[0013] Example 10. The method of Example 9, wherein the training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the brain region or at least one biomarker thereof upon exposure to at least one interface.

[0014] Example 11. The method of Example 10, wherein the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0015] Example 12. The method according to any one of Examples 8 to 10, wherein the administered NF treatment is functional magnetic resonance imaging (fMRI) neurofeedback treatment.

[0016] Example 13. The method of any one of the preceding examples, wherein said achieving comprises achieving an average reduction of at least a 6 point on the CAPS-5 scale when said administration is completed.

[0017] Example 14. The method of any one of Examples 8 to 13, wherein said selecting comprises selecting a population of patients diagnosed with chronic PTSD.

[0018] Example 15. 1. A method of treating a patient population for PTSD, comprising: Selecting a group of female patients diagnosed with PTSD and administering an NF treatment to said population; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of at least 8 weeks of said administration; A method comprising:

[0019] Example 16. The method of Example 15, wherein said administering comprises training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof.

[0020] Example 17. The method of Example 16, wherein said training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface.

[0021] Example 18. 18. The method of Example 17, wherein the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0022] Example 19. The method according to any one of Examples 15 to 17, wherein the administered NF treatment is functional magnetic resonance imaging (fMRI) neurofeedback treatment.

[0023] Example 20. The method of any one of Examples 15-19, wherein said achieving comprises achieving an average reduction of at least 6 points on the CAPS-5 scale within 3 months of said administration.

[0024] Example 21. The method of any one of Examples 15-20, wherein said achieving comprises achieving an average reduction of at least 10 points on the PTSD Checklist for DSM-5 (PCL-5) scale after a period of at least 8 weeks of said administration and / or within 3 months of said administration.

[0025] Example 22. The method of any one of Examples 15-21, wherein said selecting comprises selecting a population of female patients diagnosed with chronic PTSD.

[0026] Example 23. 1. A method of treating a patient population for PTSD, comprising: Selecting a group of male patients diagnosed with PTSD and administering an NF treatment to said population; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of at least 8 weeks of said administration; A method comprising:

[0027] Example 24. The method of Example 23, wherein said administering comprises training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof.

[0028] Example 25. The method of Example 24, wherein said training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface.

[0029] Example 26. 26. The method of Example 25, wherein the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0030] Example 27. The method according to any one of Examples 23 to 25, wherein the administered NF treatment is functional magnetic resonance imaging (fMRI) neurofeedback treatment.

[0031] Example 28. The method of any one of Examples 23-27, wherein said achieving comprises achieving an average reduction of at least 6 points on the CAPS-5 scale within 3 months of said administration.

[0032] Example 29. The method of any one of Examples 23-28, wherein said selecting comprises selecting a population of male patients diagnosed with chronic PTSD.

[0033] Example 30. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of patients diagnosed with PTSD due to non-civilian trauma; administering NF treatment to selected populations; and Achieving a mean reduction of at least 6 points on the CAPS-5 scale in a selected population after a period of at least 8 weeks of implementation; and A method comprising:

[0034] Example 31. The method of Example 30, wherein said administering comprises training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof.

[0035] Example 32. The method of Example 31, wherein said training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface.

[0036] Example 33. 33. The method of Example 32, wherein the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0037] Example 34. The method according to any one of Examples 30 to 32, wherein the administered NF treatment is functional magnetic resonance imaging (fMRI) neurofeedback treatment.

[0038] Example 35. The method of any one of Examples 30-34, wherein said achieving comprises achieving an average reduction of at least 6 points on the CAPS-5 scale within 3 months of said administration.

[0039] Example 36. The method of any one of Examples 30-35, wherein said selecting comprises selecting a population of patients diagnosed with chronic PTSD.

[0040] Example 37. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of patients diagnosed with PTSD due to civilian trauma; administering an NF treatment to said selected population; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population at least 8 weeks after said administration; A method comprising:

[0041] Example 38. The method of Example 37, wherein said administering comprises training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof.

[0042] Example 39. The method of Example 38, wherein said training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the brain region or at least one biomarker thereof upon exposure to at least one interface.

[0043] Example 40. 40. The method of Example 39, wherein the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0044] Example 41. The method according to any one of Examples 37 to 39, wherein the administered NF treatment is a neurofeedback treatment using functional magnetic resonance imaging (fMRI).

[0045] Example 42. The method of any one of Examples 37-41, wherein said achieving comprises achieving an average reduction of at least 6 points on the CAPS-5 scale within 3 months of said administration.

[0046] Example 43. The method of any one of Examples 37-42, wherein said achieving comprises achieving an average reduction of at least 10 points on the PTSD Checklist for DSM-5 (PCL-5) scale after a period of at least 8 weeks of said administration and / or within 3 months of said administration.

[0047] Example 44. The method of any one of Examples 37-43, wherein said selecting comprises selecting a population of patients diagnosed with chronic PTSD.

[0048] Example 45. 1. A method for assessing the success of NF treatment in a patient with PTSD, comprising: Selecting patients diagnosed with PTSD and administering NF treatment to the selected patient; assessing the success of the NF treatment in the patient after a period of 8 to 12 weeks of the administration; A method comprising:

[0049] Example 46. The method of Example 45, further comprising extending or ceasing said administration based on the results of said evaluation.

[0050] Example 47. The method of Example 45, further comprising extending the administration and providing additional treatment to the patient based on the results of the assessment.

[0051] Example 48. The method of Example 47, wherein the additional treatment comprises at least one of a drug treatment, psychotherapy, psychotherapy, group therapy, and at least one additional NF treatment.

[0052] Example 49. The method of any one of Examples 45-48, wherein said assessing comprises assessing the success of said NF treatment using at least one of the CAPS-5 scale, the PTSD Checklist for DSM-5 (PCL-5) scale, the Patient Health Questionnaire (PHQ-9), the Emotion Regulation Questionnaire (ERQ), and / or expert observation.

[0053] Example 50. The method of any one of Examples 45-49, wherein said administering comprises training said selected patient with said NF treatment to modulate activation of the amygdala or at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface.

[0054] Example 51. 51. The method of Example 50, wherein administering the NF treatment comprises recording EEG signals from the selected patient during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the selected patient regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0055] Example 52. 52. The method of Example 51, wherein the providing feedback includes modifying the at least one interface based on the one or more extracted signals indicative of the activity level of the amygdala or the activity level of the at least one associated brain region.

[0056] Example 53. 1. A method of treating a patient population for PTSD, comprising: Selecting a group of female patients diagnosed with PTSD and administering an NF treatment to said population; said administering includes training said selected female population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface. method.

[0057] Example 54. 54. The method of Example 53, wherein administering the NF treatment comprises recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0058] Example 55. 55. The method of Example 54, wherein the providing feedback includes modifying the at least one interface based on the one or more extracted signals indicative of the activity level of the amygdala or the activity level of the at least one associated brain region or the at least one biomarker thereof.

[0059] Example 56. The method of any one of Examples 53-55, wherein said selecting comprises selecting said population of female patients diagnosed with chronic PTSD.

[0060] Example 57. 1. A method of treating a patient population for PTSD, comprising: Selecting a group of male patients diagnosed with PTSD and administering an NF treatment to said population; said administering includes training said selected male population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface. method.

[0061] Example 58. 58. The method of Example 57, wherein administering the NF treatment comprises recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the selected population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0062] Example 59. 59. The method of Example 58, wherein the providing feedback includes modifying the at least one interface based on the one or more extracted signals indicative of the activity level of the amygdala or the activity level of the at least one associated brain region or the at least one biomarker thereof.

[0063] Example 60. The method of any one of Examples 57-59, wherein said selecting comprises selecting said population of male patients diagnosed with chronic PTSD.

[0064] Example 61. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of patients diagnosed with PTSD resulting from non-civilian trauma; administering an NF treatment to said selected population; said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface. method.

[0065] Example 62. 62. The method of Example 61, wherein administering the NF treatment comprises recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the selected population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0066] Example 63. 63. The method of Example 62, wherein the providing feedback includes modifying the at least one interface based on the one or more extracted signals indicative of the activity level of the amygdala or the activity level of the at least one associated brain region or the at least one biomarker thereof.

[0067] Example 64. The method of any one of Examples 61-63, wherein said selecting comprises selecting said population of patients diagnosed with chronic PTSD.

[0068] Example 65. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of patients diagnosed with PTSD resulting from civilian trauma; administering an NF treatment to said selected population; said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface. method.

[0069] Example 66. 66. The method of Example 65, wherein administering the NF treatment comprises recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the selected population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

[0070] Example 67. 67. The method of Example 66, wherein the providing feedback includes modifying the at least one interface based on the one or more extracted signals indicative of the activity level of the amygdala or the activity level of the at least one associated brain region or the at least one biomarker thereof.

[0071] Example 68. The method of any one of Examples 65-67, wherein said selecting comprises selecting said population of patients diagnosed with chronic PTSD.

[0072] Example 69. 1. A system for administering neurofeedback therapy for the treatment of PTSD, comprising: at least one user interface configured to provide at least one notification; a control unit having a memory and a control circuit; the memory stores at least one protocol of neurofeedback (NF) therapy or notification of such protocol; The control circuitry is configured to administer the NF treatment to the PTSD patient based on the at least one protocol stored in the memory or a notification of the protocol, and to signal the at least one user interface to generate a notification with information for evaluating the results of the NF treatment within a period of 8 to 12 weeks from the start of administration of the NF treatment. system.

[0073] Example 70. 70. The system of Example 69, wherein the control circuitry is configured to receive an input signal including information regarding a result of the assessment and to signal the at least one user interface to generate a notification with information including a suggestion to modify the at least one NF treatment protocol or to discontinue administration of the NF treatment in response to the result of the assessment.

[0074] Example 71. 70. The system of Example 69, wherein the memory stores a plurality of protocols for the NF treatment, and the control circuitry is configured to receive an input signal including information regarding a result of the evaluation and to signal the at least one user interface to generate a notification with information including a suggestion to replace the at least one protocol for the NF treatment with a different protocol in response to the result of the evaluation.

[0075] Example 72. 70. The system of Example 69, wherein the system includes at least one remote device that stores a plurality of protocols for the NF treatment, the control unit comprising communication circuitry configured to communicate with the at least one remote device, the control circuitry configured to receive an input signal including information regarding a result of the evaluation, and to signal the at least one user interface to generate a notification with information including a suggestion to replace the at least one protocol for the NF treatment with a different protocol from the plurality of protocols stored in the at least one remote device in response to the result of the evaluation.

[0076] Example 73. 73. The system of Example 72, wherein the at least one remote device comprises at least one of a remote computer, a server, a cloud storage device, and a cloud storage and processing device.

[0077] Example 74. The control unit comprises an EEG recording unit and a patient interface configured to record electrical signals from one or more electrodes placed on the subject's head, and the control circuitry comprises: transmitting a signal to a patient interface to present an interface stored in the memory to the PTSD patient, the interface selected to increase amygdala activity or activity of at least one associated brain region or at least one biomarker thereof in the subject; measuring an EEG signal based on the electrical signal received by the EEG recording unit; using the measured EEG signals and at least one algorithm stored in a memory and / or an electrical fingerprint (EFP) of the amygdala or the at least one associated brain region or the at least one biomarker thereof to detect changes in activity of the amygdala or changes in activity of the at least one associated brain region or changes in the at least one biomarker thereof; modifying the presentation of the interface to the PTSD patient in response to the detected change in activity. The system of any one of Examples 69 to 73, configured as follows:

[0078] Example 75. 1. A method for assessing the success of NF treatment in a patient with PTSD, comprising: receiving results of at least one assessment of the PTSD patient conducted after initiation of the NF treatment in the PTSD patient; determining a relationship between the evaluation results and an expected evaluation result; generating a notification based on the determined relationship; and A method comprising:

[0079] Example 76. 76. The method of Example 75, wherein the determining includes determining that the evaluation result is lower than the expected result, and the generating includes generating the notification with instructions to modify at least one parameter of the NF treatment and administer at least one additional NF treatment session of the NF treatment using the modified at least one NF treatment parameter.

[0080] Example 77. 77. The method of Example 76, wherein the at least one NF treatment parameter includes a duration of the NF treatment session, a number of additional NF treatment sessions, a type and / or content of a visual interface presented to the patient during the NF treatment session, and an analysis performed on EEG signals recorded from the subject's brain during the NF treatment session, the analysis being performed to detect modulation of activity of at least one of a limbic network, at least one limbic brain region, and an amygdala brain region based solely on the EEG signals.

[0081] Example 78. 78. The method of any one of Examples 76 or 77, wherein the generated notification includes instructions to combine the NF treatment using the modified parameters with at least one different treatment.

[0082] Example 79. The method of Example 75, wherein the determining includes determining that the assessment result is lower than the expected result, and the generating includes generating the notification with instructions to replace the NF treatment with at least one different treatment or to continue the NF treatment in combination with the at least one different treatment.

[0083] Example 80. 80. The method of any one of Examples 78 or 79, wherein the at least one different treatment comprises at least one of cognitive behavioral treatment (CBT), psychotherapy, psychiatric treatment, and / or pharmacotherapy.

[0084] Example 81. 76. The method of Example 75, wherein the determining includes determining that the assessment result is lower than the expected result, and the generating includes generating the notification with instructions to administer one or more additional NF treatment sessions or to discontinue administration of the NF treatment.

[0085] Example 82. 81. The method of any one of Examples 75-80, wherein the at least one assessment comprises the Structured Interview Scale for PTSD for DSM-5 (CAPS-5) scale, and the expected outcome assessment comprises at least a 6-point reduction in the CAPS-5 scale in the patient after at least 8 weeks of NF treatment.

[0086] Example 83. The method of any one of Examples 75-82, wherein the at least one assessment includes the PTSD Checklist for DSM-5 (PCL-5) scale, and the predicted outcome includes at least a 9-point reduction in the PCL-5 scale after at least 8 weeks of NF treatment.

[0087] Example 84. 84. The method of any one of Examples 75-83, comprising providing the generated notification to a supervisor of the NF treatment in the patient.

[0088] Example 85. 1. A system for assessing the success of a NF treatment, comprising: a memory for storing results of at least one assessment of the PTSD patient conducted after initiation of the NF treatment in the PTSD patient, and a predicted outcome of the assessment; control circuitry configured to determine a relationship between the stored result of the at least one evaluation and the stored expected outcome, and to generate a notification in response to the determined relationship; Including, the system.

[0089] Example 86. 86. The system of Example 85, wherein the control circuitry is configured to determine that the evaluation result is lower than the expected result and to generate a notification with instructions to modify at least one parameter of the NF treatment and to administer at least one additional NF treatment session of the NF treatment to the patient using the modified at least one NF treatment parameter.

[0090] Example 87. 87. The system of Example 86, wherein the notification generated by the control circuitry includes instructions to modify the at least one NF treatment parameter including at least one of a duration of a NF treatment session, a number of additional NF treatment sessions, a type and / or content of a visual interface presented to the patient during a NF treatment session, and an analysis performed on EEG signals recorded from the subject's brain during the NF treatment session, the analysis being performed to detect modulation of activity of at least one of a limbic network, at least one limbic brain region, and an amygdala brain region based solely on the EEG signals.

[0091] Example 88. 88. The system of any one of Examples 86 or 87, wherein the generated notification includes instructions to combine the NF therapy using the modified parameters with at least one additional therapy.

[0092] Example 89. 86. The system of Example 85, wherein the control circuitry is configured to determine that the evaluation result is lower than the expected result and to generate the notification with instructions to replace the NF treatment with at least one additional treatment or to continue the NF treatment in combination with the at least one additional treatment.

[0093] Example 90. 90. The system of any one of Examples 88 or 89, wherein the at least one additional treatment includes at least one of cognitive behavioral therapy (CBT), psychotherapy, psychiatric treatment, and / or medication.

[0094] Example 91. 86. The system of Example 85, wherein the control circuitry is configured to determine that the assessment result is lower than the expected result and to generate a notification with instructions to provide one or more additional NF treatment sessions or to discontinue administration of the NF treatment.

[0095] Example 92. The system of any one of Examples 85-91, wherein the assessment results stored in the memory include results from a Structured Interview Scale for PTSD for DSM-5 (CAPS-5) scale, and the predicted assessment results stored in the memory include a mean 6-point reduction in at least one of the CAPS-5 scales in the patient after at least 8 weeks of NF treatment.

[0096] Example 93. 93. The system of any one of Examples 85-92, wherein the assessment results stored in the memory include results of a PTSD Checklist for DSM-5 (PCL-5) scale, and the predicted assessment results stored in the memory include a mean 9-point reduction in at least one of the PCL-5 scales in the patient after at least 8 weeks of the NF treatment.

[0097] Example 94. The system of any one of Examples 85-93, wherein the system includes a communication circuit, the system receives the results of the at least one evaluation using the communication circuit, and the control circuit signals the communication circuit to provide the generated notification to a remote device.

[0098] Example 95. 1. A method for assessing the success of NF treatment in a group of PTSD patients, comprising: receiving results of at least one assessment in the group of PTSD patients conducted after initiation of the NF treatment in the PTSD patients; determining a relationship between the evaluation results and an expected evaluation result; generating a notification based on the determined relationship; and A method comprising:

[0099] Example 96. 96. The method of Example 95, further comprising processing the received results to generate an individual assessment result for at least one subclass of the group of PTSD patients, and wherein determining includes determining a relationship between the individual assessment result and the predicted assessment result for the at least one subclass of PTSD patients.

[0100] Example 97. The method of Example 96, wherein the at least one subclass of PTSD patients includes at least one of female PTSD patients, male PTSD patients, PTSD patients whose PTSD is caused by civilian trauma, and PTSD patients whose PTSD is caused by non-civilian trauma.

[0101] Example 98. The method of any one of Examples 96 or 97, wherein the determining includes determining that the evaluation result for the at least one subclass is lower than the expected result, and the generating includes generating a notice with instructions including at least one of: instructions to modify at least one parameter of the NF treatment, instructions to replace an existing protocol for the NF treatment with a different protocol, instructions to discontinue the NF treatment, and instructions to combine the NF treatment with at least one additional treatment.

[0102] Example 99. The method of any one of Examples 95-98, wherein the at least one assessment includes at least one of the PTSD Checklist for DSM-5 (PCL-5) scale and the Diagnostic and Statistical Approach to Posttraumatic Stress Disorder (CAPS-5) scale.

[0103] Example 100. 1. A system for assessing the success of a NF treatment, comprising: a memory for storing results of at least one assessment performed on a group of PTSD patients after initiation of the NF treatment in the PTSD patients, and a predicted outcome of the assessment; control circuitry configured to determine a relationship between the stored result of the at least one evaluation and the stored expected outcome, and to generate a notification in response to the determined relationship; Including, the system.

[0104] Example 101. The system of Example 100, wherein the control circuitry is configured to process the received results to generate individual assessment results for at least one subclass of the group of PTSD patients, and to determine a relationship between the individual assessment results for the at least one subclass of PTSD patients and the expected assessment results.

[0105] Example 102. The system of Example 101, wherein the at least one subclass of PTSD patients includes at least one of female PTSD patients, male PTSD patients, PTSD patients whose PTSD is caused by civilian trauma, and PTSD patients whose PTSD is caused by non-civilian trauma.

[0106] Example 103. The system of any one of Examples 101 or 102, wherein determining includes determining that the evaluation result for the at least one subclass is lower than the expected result, and generating includes generating a notification with instructions including at least one of: instructions to modify at least one parameter of the NF treatment, instructions to replace an existing NF treatment protocol with a different protocol for the NF treatment, instructions to discontinue the NF treatment, and instructions to combine the NF treatment with at least one additional treatment.

[0107] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used to practice or test embodiments of the present invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will prevail. In addition, the materials, methods, and examples are merely illustrative and are not necessarily intended to be limiting.

[0108] As will be appreciated by those skilled in the art, some embodiments of the present invention may be embodied as a system, a method, or a computer program product. Accordingly, some embodiments of the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, microcode, etc.), or an embodiment combining software and hardware aspects generally referred to herein as a "circuit," "module," or "system." Furthermore, some embodiments of the present invention may take the form of a computer program product embodied in one or more computer-readable mediums having computer-readable program code embodied thereon. Implementation of the method and / or system of some embodiments of the present invention may involve performing and / or completing selected tasks manually, automatically, or a combination thereof. Furthermore, depending on the actual equipment and apparatus of some embodiments of the method and / or system of the present invention, some selected tasks may be implemented by hardware, software, or firmware, and / or a combination thereof (e.g., using an operating system).

[0109] For example, hardware for performing selected tasks according to some embodiments of the present invention may be implemented as a chip or circuit. As software, selected tasks according to some embodiments of the present invention may be implemented as a plurality of software instructions executed by a computer using any suitable operating system. In exemplary embodiments of the present invention, one or more tasks according to some exemplary embodiments of the methods and / or systems described herein are performed by a data processor, such as a computing platform for executing a plurality of instructions. Optionally, the data processor includes volatile memory for storing instructions and / or data, and / or non-volatile storage, such as a magnetic hard disk and / or removable media, for storing instructions and / or data. Optionally, a network connection is also provided. A display device and user input devices, such as a keyboard and mouse, are also optionally provided.

[0110] Some embodiments of the present invention may utilize any combination of one or more computer-readable media. The computer-readable medium may be a computer-readable signal medium or a computer-readable storage medium. The computer-readable storage medium may be, for example, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination thereof. More specific examples (non-exclusive list) of computer-readable storage media include an electrical connection having one or more wires, a portable computer disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disk read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination thereof. As used herein, a computer-readable storage medium refers to any tangible medium that can contain or store a program for use by or in connection with an instruction execution system, an instruction execution apparatus, or an instruction execution device.

[0111] A computer-readable signal medium may include a propagated data signal having computer-readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including electromagnetic, optical, or any suitable combination thereof. A computer-readable signal medium may be any computer-readable medium, other than a computer-readable storage medium, that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, instruction execution apparatus, or instruction execution device.

[0112] The program code and / or data embodied in the computer readable medium may be transmitted using any suitable medium, such as wireless, wire, fiber optic cable, RF, etc., or any suitable combination thereof.

[0113] Computer program code for carrying out operations of some embodiments of the present invention may be written in any combination of one or more programming languages, including object-oriented programming languages ​​such as Java, Smalltalk, C++, etc., and conventional procedural programming languages ​​such as the "C" programming language. The program code may run entirely on the user's computer as a standalone software package, partially on the user's computer, partially on the user's computer and partially on a remote computer, or entirely on a remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer via any type of network, including a local area network (LAN) or a wide area network (WAN), or may be connected to an external computer (e.g., via the Internet using an Internet Service Provider).

[0114] Some embodiments of the present invention may be described below with reference to flowcharts and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the present invention. It should be understood that each block of the flowcharts and / or each block of the block diagrams, and combinations of each block of the flowcharts and / or each block of the block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, a special-purpose computer, or other programmable data processing apparatus, and executed as instructions executed by the processor of the computer or other programmable data processing apparatus to form means for implementing the functions / acts specified in the flowcharts and / or block diagrams or blocks.

[0115] These computer program instructions may be stored on a computer-readable medium that can inform a computer, other programmable data processing apparatus, or other device to perform certain operations, such that the instructions stored on the computer-readable medium result in an article of manufacture that includes instructions that perform the particular functions / operations of the flowcharts and / or block diagrams.

[0116] The computer program instructions may be loaded into a computer, other programmable data processing apparatus, or other device and cause the computer, other programmable apparatus, or other device to perform a series of operational steps to create a computer-implemented process, such that instructions executed on the computer or other programmable apparatus provide processing to implement the particular functions / operations of the flowcharts and / or block diagrams.

[0117] Some of the methods described herein are generally designed to be used solely by a computer and may not be feasible or practical to perform purely manually by a human expert. A human expert wishing to manually perform similar tasks, such as assessing biomarker values ​​in real time and controlling the behavior of a digital or interactive interface in real time, may be expected to use an entirely different method, such as leveraging specialized knowledge and / or the pattern recognition capabilities of the human brain, that is far more efficient than manually performing the steps of the methods described herein.

[0118] Certain embodiments of the present invention are described herein, by way of example only, with reference to the accompanying drawings. It is emphasized that the details shown below, with particular reference to the drawings, are for the purposes of illustration and for the purpose of providing a detailed description of embodiments of the present invention. Similarly, from viewing the description in conjunction with the drawings, it will become apparent to those skilled in the art how embodiments of the present invention may be practiced. [Brief explanation of the drawings]

[0119] [Figure 1] 1 is a general flowchart of a PTSD neurofeedback (NF) treatment process, according to some exemplary embodiments of the present invention. [Figure 2] 1 is a flowchart of an NF treatment session, according to some exemplary embodiments of the present invention. [Figure 3] FIG. 1 is a block diagram of a system for administering PTSD NF treatment, according to some exemplary embodiments of the present invention. [Figure 4A] 1 is a flowchart of a PTSD NF treatment process for assessing a patient's condition between 8 and 12 weeks after beginning administration of NF treatment sessions, according to some exemplary embodiments of the present invention. [Figure 4B]1 is a flowchart of a process for selecting a subpopulation of female subjects for NF treatment, according to some exemplary embodiments of the present invention. [Figure 4C] 1 is a flowchart of a process for selecting a subpopulation of patients diagnosed with PTSD resulting from civilian trauma for NF treatment, according to some exemplary embodiments of the present invention. [Figure 5A] 1 is a flowchart of a PTSD NF treatment process implemented in a clinical trial, according to some exemplary embodiments of the present invention. [Figure 5B] FIG. 1 is a schematic diagram illustrating the use of an Electrical Fingerprint (EFP) model to determine amygdala activity levels during PTSD NF treatments implemented in clinical trials, according to some exemplary embodiments of the present invention. [Figure 5C] 1 is a schematic block diagram of a device for assessing the effect of NF treatment on the condition of a patient receiving treatment, according to some exemplary embodiments of the present invention. FIG. [Figure 5D] 1 is a flowchart of a general evaluation process according to some embodiments of the present invention. [Figure 5E] 10 is a flowchart of a detailed evaluation process according to some example embodiments of the present invention. [Figure 5F] 1 is a flowchart of a process for assessing the effectiveness of NF treatment for a particular patient population, according to some exemplary embodiments of the present invention. [Figure 6A] 1 is a graph showing the mean change in scores on the Structured Interview for PTSD Adapted from DSM-5 (CAPS-5) scale during the clinical trial. [Figure 6B] 1 is a graph showing the mean change in scores for criterion B of the CAPS-5 scale during the clinical trial. [Figure 6C] 1 is a graph showing the mean change in scores for criterion C of the CAPS-5 scale during the clinical trial. [Figure 6D] 1 is a graph showing the mean change in scores on criterion D of the CAPS-5 scale during the clinical trial. [Figure 6E] 1 is a graph showing the mean change in scores for criterion E of the CAPS-5 scale during the clinical trial. [Figure 6F] 1 is a graph showing the mean change in score on criterion G of the CAPS-5 scale during the clinical trial. [Figure 7A] 1 is a graph showing the mean change in CAPS-5 scale scores during clinical trials in patients with PTSD due to civilian trauma. [Figure 7B] FIG. 1 is a graph showing the mean change in scores on criterion B of the CAPS-5 scale during clinical trials in patients with PTSD due to civilian trauma. [Figure 7C] FIG. 1 is a graph showing the mean change in scores on criterion C of the CAPS-5 scale during clinical trials in patients with PTSD due to civilian trauma. [Figure 7D] FIG. 1 is a graph showing the mean change in scores on criterion D of the CAPS-5 scale during clinical trials in patients with PTSD due to civilian trauma. [Figure 7E] FIG. 1 is a graph showing the mean change in scores on Criterion E of the CAPS-5 scale during clinical trials in patients with PTSD due to civilian trauma. [Figure 7F] FIG. 1 is a graph showing the mean change in scores on Criterion G of the CAPS-5 scale during clinical trials in patients with PTSD due to civilian trauma. [Figure 8A] 1 is a graph showing the mean change in scores on the PCL-5 scale during the clinical trial. [Figure 8B] FIG. 1 is a graph showing the mean change in scores on the PCL-5 scale during clinical trials in patients with PTSD due to civilian trauma. [Figure 9A] 1 is a graph showing the mean change in scores on the PHQ-9 scale during the clinical trial. [Figure 9B] FIG. 1 is a graph showing the mean change in scores on the PHQ-9 scale during clinical trials in patients with PTSD due to civilian trauma. DETAILED DESCRIPTION OF THE INVENTION

[0120] In some embodiments, the present invention relates to the treatment of stress disorders, particularly (but not exclusively) to the treatment of post-traumatic stress disorder (PTSD).

[0121] One aspect of some embodiments relates to achieving at least a 6-point reduction on the Structured Interview Scale for PTSD (CAPS-5) for DSM-5 after neurofeedback (NF) treatment administered to a human subject over a period ranging from 8 to 12 consecutive weeks. In some embodiments, the at least 6-point reduction is achieved in a human subject diagnosed with PTSD who has undergone NF treatment. In some embodiments, the at least 6-point reduction on the CAPS-5 scale is achieved after NF treatment (also referred to herein as NF training) lasting between 8 and 12 weeks, e.g., 8 consecutive weeks and 12 consecutive weeks. In some embodiments, the at least 6-point reduction on the CAPS-5 includes at least a 7-point reduction, at least a 10-point reduction, at least a 15-point reduction, at least a 20-point reduction, or any intermediate, smaller, or larger value.

[0122] According to some exemplary embodiments, in some embodiments, the human subject is diagnosed with chronic PTSD. For example, the human subject has had symptoms of PTSD for 1 month, at least 6 months, at least 10 months, at least 12 months, at least 14 months, at least 16 months, at least 24 months, or any intermediate, shorter, or longer period. Alternatively or additionally, the human subject is diagnosed with chronic PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) or earlier or later editions.

[0123] According to some embodiments, the human subject is a female subject. Alternatively or additionally, the human subject is diagnosed with PTSD resulting from civilian trauma.

[0124] According to some exemplary embodiments, NF treatment includes monitoring activity in at least one limbic brain region (e.g., the amygdala) or at least one biomarker associated with that activity and sending a signal to the subject based on the monitored activity. In some embodiments, activity in the at least one limbic brain region is monitored using at least one EEG signal recorded from electrodes placed on the subject's head, as described, for example, in International Patent Application Publication No. WO2012104853A2, filed February 2, 2012, and International Patent Application Publication No. WO2020121299A1, filed December 9, 2019, the contents of which are incorporated by reference in their entireties.

[0125] According to some exemplary embodiments, NF treatment is administered at a clinic or office outside the subject's home and / or at the subject's home. In some embodiments, NF treatment includes at least two treatment sessions per week.

[0126] One aspect of some embodiments relates to treating a human subject diagnosed with PTSD with NF therapy for an 8- to 12-week period, e.g., an 8- to 10-week period, an 8- to 11-week period, an 8- to 9-week period, a 10- to 12-week period, or any intermediate, shorter, or longer period. In some embodiments, a reduction of at least 6 points on the Structured Interview Scale for PTSD (CAPS-5) for DSM-5 is achieved within 3 months of the end of NF therapy (e.g., from the last treatment session of NF therapy). In some embodiments, the reduction in CAPS-5 is achieved within 2 months, within 1 month, between 1 month and 3 months, or within any intermediate, shorter, or longer period of time after the end of NF therapy.

[0127] According to some exemplary embodiments, a reduction of at least 6 points on the CAPS-5 scale is achieved at the end of NF treatment, e.g., within 2 months of the last treatment session of NF treatment. In some embodiments, a reduction of at least 6 points on the CAPS-5 scale is achieved when administration of NF treatment has ended, e.g., after an 8-12 week period of administration of NF treatment.

[0128] According to some exemplary embodiments, the human subject is diagnosed with chronic PTSD, e.g., a human subject having symptoms of PTSD for 1 month, at least 6 months, at least 10 months, at least 12 months, at least 14 months, at least 16 months, at least 24 months, or any intermediate, shorter, or longer period. Alternatively or additionally, the human subject is diagnosed with chronic PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) or earlier or later editions.

[0129] One aspect of some embodiments relates to achieving at least a 6-point reduction on the Structured Interview Scale for PTSD (CAPS-5) for DSM-5 after neurofeedback (NF) treatment administered to human subjects over a period of at least 8 weeks. In some embodiments, the at least 6-point reduction is achieved in a population of female human subjects diagnosed with PTSD who have undergone NF treatment. In some embodiments, the population of female human subjects is selected for NF treatment. This selection is based, for example, on a prediction that the selected population will be successful in achieving at least a 6-point reduction on the CAPS-5 after 8 weeks of NF treatment. In some embodiments, a female human subject is diagnosed with chronic PTSD, for example, having had symptoms of PTSD for at least 1 month, at least 14 months, at least 16 months, at least 24 months, or any intermediate, shorter, or longer period. Alternatively or additionally, the female human subject is diagnosed with chronic PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) or earlier or later editions. Optionally, female human subjects are diagnosed with PTSD resulting from at least one civilian traumatic event (e.g., sexual trauma, accident, and violence) or PTSD resulting from a non-civilian trauma.

[0130] One aspect of some embodiments relates to achieving at least a 6-point reduction on the Structured Interview for PTSD (CAPS-5) for DSM-5 after neurofeedback (NF) treatment administered to human subjects over a period of at least 8 weeks. In some embodiments, the at least 6-point reduction is achieved in a population of male human subjects diagnosed with PTSD who have undergone NF treatment. In some embodiments, the population of male human subjects is selected for NF treatment. This selection is based, for example, on a prediction that the selected population will be successful in achieving at least a 6-point reduction on the CAPS-5 after 8 weeks of NF treatment. In some embodiments, for example, a male human subject is diagnosed with chronic PTSD after having symptoms of PTSD for at least 1 month, at least 14 months, at least 16 months, at least 24 months, or any intermediate, shorter, or longer period. Alternatively or additionally, a female human subject is diagnosed with chronic PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) or earlier or later editions. Optionally, male human subjects are diagnosed with PTSD resulting from at least one civilian traumatic event (e.g., sexual trauma, accident, and violence), or PTSD resulting from a non-civilian trauma.

[0131] One aspect of some embodiments relates to achieving at least a 6-point reduction on the Structured Interview Scale for PTSD (CAPS-5) for DSM-5 after neurofeedback (NF) treatment administered to human subjects over a period of at least 8 weeks. In some embodiments, the at least 6-point reduction is achieved in a population of human subjects diagnosed with PTSD resulting from civilian trauma and receiving NF treatment. In some embodiments, the population of human subjects is selected for NF treatment. This selection is based, for example, on a prediction that the selected population will be successful in achieving at least a 6-point reduction on the CAPS-5 after 8 weeks of NF treatment. In some embodiments, a human subject is diagnosed with chronic PTSD, for example, a human subject who has had symptoms of PTSD for at least 1 month, at least 14 months, at least 16 months, at least 24 months, or any intermediate, shorter, or longer period. Alternatively or additionally, the human subject is diagnosed with chronic PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).

[0132] One aspect of some embodiments relates to achieving at least a 6-point reduction on the Structured Interview for PTSD (CAPS-5) for DSM-5 after neurofeedback (NF) treatment administered to human subjects over a period of at least 8 weeks. In some embodiments, the at least 6-point reduction is achieved in a population of human subjects diagnosed with PTSD resulting from non-civilian trauma and receiving NF treatment. In some embodiments, the population of human subjects is selected for NF treatment. This selection is based, for example, on a prediction that the selected population will be successful in achieving at least a 6-point reduction on the CAPS-5 after 8 weeks of NF treatment. In some embodiments, a human subject is diagnosed with chronic PTSD, for example, a human subject who has had symptoms of PTSD for at least 1 month, at least 14 months, at least 16 months, at least 24 months, or any intermediate, shorter, or longer period. Alternatively or additionally, the human subject is diagnosed with chronic PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).

[0133] One aspect of some embodiments relates to administering NF treatment to a selected population of female patients diagnosed with PTSD. In some embodiments, administering the NF treatment includes training the selected population of women using the NF treatment to modulate amygdala activation upon exposure to at least one interface (e.g., a stressor). In some embodiments, the patient population is selected for the NF treatment. This selection is based on a prediction that the selected population will be successful in achieving at least a 6-point reduction in the CAPS-5 score after at least 8 weeks of NF treatment and within 3 months after completion of the NF treatment, e.g., as shown in Tables A and B and the results of clinical trials. In some embodiments, the at least one interface includes a visual interface and / or an audio interface. Optionally, the at least one interface is selected to increase the subject's perception of stress when presented to the subject.

[0134] One aspect of some embodiments relates to administering NF therapy to a selected population of male patients diagnosed with PTSD. In some embodiments, administering NF therapy includes training the selected male population with NF therapy to modulate amygdala activation upon exposure to at least one interface. In some embodiments, the patient population is selected for NF therapy, the selection being based, for example, on a prediction that the selected population will be successful in achieving at least a 6-point reduction in CAPS-5 scores after 8 weeks of NF therapy.

[0135] One aspect of some embodiments relates to administering NF treatment to a selected population of patients diagnosed with PTSD resulting from non-civilian trauma. In some embodiments, administering the NF treatment includes training the selected population with the NF treatment to modulate amygdala activation upon exposure to at least one interface. In some embodiments, the patient population is selected for NF treatment, the selection being based, for example, on a prediction that the selected population will be successful in achieving at least a 6-point reduction in CAPS-5 scores after 8 weeks of NF treatment.

[0136] One aspect of some embodiments relates to administering NF therapy to a selected population of patients diagnosed with PTSD resulting from civilian trauma. In some embodiments, administering NF therapy involves training the selected population with NF therapy to modulate amygdala activation upon exposure to at least one interface. In some embodiments, the patient population is selected for NF therapy, based, for example, on a prediction that the selected population will achieve a reduction of at least 6 points on the CAPS-5 after 8 weeks of NF therapy.

[0137] One aspect of some embodiments relates to assessing the outcome of a NF treatment used to treat a human subject diagnosed with PTSD after a period of between 8 and 12 consecutive weeks from the initiation of the NF treatment. In some embodiments, the outcome of the NF treatment is assessed using CAPS-5. Alternatively or additionally, the outcome of the NF treatment is assessed using one or more CAPS-5 criteria. Alternatively or additionally, the outcome of the NF treatment is assessed using the PTSD Checklist for DSM-5 (PCL-5). Alternatively or additionally, the outcome of the NF treatment is assessed using the Patient Health Questionnaire-9 (PHQ-9).

[0138] According to some embodiments, a treatment regime provided to a PTSD subject, including NF treatment, is modified based on the assessment results. In some embodiments, modifying the treatment regime includes continuing NF treatment for one or more additional NF treatment sessions or one or more additional weeks. Alternatively, modifying the treatment regime includes discontinuing NF treatment. Alternatively, modifying the treatment regime includes replacing or combining NF treatment with at least one different treatment (e.g., medication, psychological treatment, and group therapy). Alternatively, modifying the treatment regime includes adding a future NF treatment session.

[0139] One aspect of some embodiments relates to a system for administering NF treatment configured to provide a notification with information for evaluating the success of the NF treatment at least 8 weeks after initiation of the NF treatment, hi some embodiments, the system is configured to provide a notification with information for evaluation within a period of 8 to 12 weeks after initiation of the NF treatment.

[0140] According to some embodiments, the system, e.g., the control circuitry of the system, is configured to receive input including the results of the assessment and provide a notification with information on how to modify an existing NF treatment protocol according to the results of the assessment. Alternatively, the system is configured to provide a notification with a suggestion to replace the existing NF treatment protocol with a different NF treatment protocol according to the results of the assessment. Alternatively, the system is configured to provide a notification with a suggestion to discontinue or extend delivery of the existing NF treatment protocol according to the results of the assessment.

[0141] Alternatively, the system is configured to provide a notification with a suggestion to combine the provision of the existing NF treatment protocol with additional treatment according to the assessment results, in some embodiments, the additional treatment includes at least one of pharmacotherapy, psychological treatment, psychiatric treatment, and group therapy.

[0142] According to some embodiments, NF treatment administered to a PTSD patient includes presenting at least one interface to the patient. In some embodiments, the at least one interface is selected to increase activity of the amygdala or at least one associated brain region (e.g., at least one brain region of the limbic system) or at least one biomarker thereof (e.g., at least one biomarker of amygdala activity or at least one associated brain region activity). In some embodiments, the at least one biomarker includes a physiological marker, such as heart rate, blood pressure, skin conductance, and sweating. In some embodiments, the at least one biomarker includes at least one electrical fingerprint (EFP) (e.g., an EFP model of at least one limbic brain region), such as the EFP models described in International Patent Application Publication No. WO2012104853A2, filed February 2, 2012, and International Patent Application Publication No. WO2020121299A1, filed December 9, 2019, the contents of which are incorporated by reference in their entireties. In some embodiments, the at least one interface is presented to the patient visually, optionally in combination with an audio signal. In some embodiments, EEG signals are recorded from the subject's brain using one or more electrodes placed on the subject's head. In some embodiments, the recorded EEG signals are processed using at least one algorithm and / or at least one EFP to extract a signal or indicator indicative of amygdala activity or activity of at least one related brain region, or a biomarker thereof. In some embodiments, the EEG signals are recorded and processed while the patient is exposed to the at least one interface.

[0143] According to some embodiments, the system provides feedback to the patient indicating the activity level of the amygdala or at least one related brain region based on the extracted signal. Optionally, this feedback is provided online, for example, by modifying at least one interface presented to the patient while the patient is exposed to the at least one interface. As used herein, the term "online" refers to a delay from the recording of the EEG signal of up to 20 seconds, up to 15 seconds, up to 10 seconds, up to 5 seconds, up to 2 seconds, or an intermediate, shorter, or longer delay.

[0144] According to some embodiments, the at least one interface includes a visual and / or audio interface that is presented to the patient using at least one of a display, a virtual reality device, an augmented reality device, or other visualization device.

[0145] According to some exemplary embodiments, NF treatment, e.g., NF training, is administered to a patient without the need for the use of an fMRI device.

[0146] One aspect of some embodiments relates to assessing the success of NF treatment for a subject after initiation of NF treatment, e.g., after at least one session of NF treatment or after at least one week of NF treatment. In some embodiments, this assessment is based on the results of at least one rating scale measured after at least one session or at least one week after initiation of NF treatment. In some embodiments, the assessment of treatment success is based on a relationship between the results of the rating scale measurement and stored results. In some embodiments, the stored results include previous results of rating scales previously measured for the same subject. Alternatively or additionally, the stored results include target results indicating a target level of success for NF treatment.

[0147] According to some embodiments, the NF treatment or overall treatment for a particular subject is modified based on the ratio determined between the measurement result of the rating scale and the stored result or indicator thereof. In some embodiments, modifying the NF treatment includes modifying at least one parameter of the NF treatment and, optionally, administering at least one additional NF treatment session to the subject or a different subject using the modified parameters. Alternatively, modifying the NF treatment includes discontinuing the NF treatment or combining the NF treatment with at least one additional treatment.

[0148] According to some embodiments, the success assessment is performed by a device that optionally communicates with a different device administering the NF treatment. Alternatively, the assessment is performed by the same device or system administering the NF treatment. In some embodiments, the device automatically modifies the treatment administered to the subject or a different subject. Alternatively, the device generates at least one notification with suggestions (e.g., recommendations) on how to modify the treatment. In some embodiments, the assessment scale includes at least one of CAPS-5, PCL-5, and PHQ-9, and the measured outcome includes a score on the assessment scale.

[0149] One aspect of some embodiments relates to assessing the success of NF treatment in a group of subjects after initiation of NF treatment, e.g., after at least one session of NF treatment or after at least one week of NF treatment. In some embodiments, this assessment is based on the results of at least one rating scale administered by the group of subjects after initiation of NF treatment. In some embodiments, the assessment of treatment success is based on a determined relationship between the results of the rating scale and stored results. In some embodiments, the stored results include previous results of rating scales previously measured for the same subject and / or each subject. Alternatively or additionally, the stored results include a target result indicating a target level of success for NF treatment.

[0150] According to some embodiments, the NF treatment for one or more subjects belonging to the group of subjects is modified based on the determined relationship. Alternatively or additionally, the results of the rating scale for the group of subjects are further processed (e.g., categorized) based on the determined relationship to isolate the results for one or more subpopulations included in the group of subjects. In some embodiments, the relationship between the results of the subpopulation of subjects and the stored results is determined, for example, to identify whether a particular subpopulation showed better results on the rating scale relative to the overall larger group of subjects. In some embodiments, the NF treatment for one or more subjects belonging to the particular subpopulation is modified, for example, to increase the effectiveness of the NF treatment in subjects in the particular subpopulation.

[0151] Before describing at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of elements and / or methods set forth in the following description and / or illustrated in the drawings and / or examples. The invention is capable of other embodiments and of being practiced or carried out in various ways.

[0152] An exemplary general process for treating PTSD

[0153] Subjects diagnosed with PTSD receive NF treatment over several weeks to reduce their scores on the CAPS-5 scale after treatment, in some embodiments, the reduction achieved indicates a significant clinical improvement in their PTSD condition.

[0154] According to some exemplary embodiments of the present invention, as shown in FIG. 1, a process for treating a subject diagnosed with PTSD with NF is illustrated.

[0155] According to some exemplary embodiments, a subject is diagnosed with a stress disorder, e.g., PTSD, at block 102. In some embodiments, the subject is diagnosed with PTSD according to at least one criterion of the DSM-V. Optionally, the subject is diagnosed with chronic PTSD. For example, the subject experiences one or more PTSD symptoms for at least one month, e.g., at least 14 months, at least 18 months, at least 24 months, or for an intermediate, short, or long period of time since the subject first experienced a PTSD symptom. In some embodiments, the diagnosis is made using one or more diagnostic tools (e.g., questionnaires). Alternatively or additionally, the diagnosis is made based on observation and / or expert experience.

[0156] According to some exemplary embodiments, the traumatic event is a non-civilian traumatic event, for example, a traumatic event occurring during or in response to combat operations.

[0157] According to some exemplary embodiments, the subject's suitability for NF treatment is optionally identified at block 104. In some embodiments, identifying the subject's suitability includes identifying the subject's likelihood of achieving a reduction in their score on the CAPS-5 scale after NF treatment. In some embodiments, identifying the subject's suitability includes identifying the subject's likelihood of achieving at least a 6-point reduction on the CAPS-5 scale, e.g., at least 6 points, at least 10 points, or an intermediate, smaller, or larger reduction, after at least 8 weeks, e.g., at least 8 consecutive weeks, of NF treatment. Alternatively or additionally, identifying the subject's suitability includes identifying the subject's likelihood of achieving at least a 6-point reduction on the CAPS-5 scale after 8 to 12 consecutive weeks of NF treatment.

[0158] According to some exemplary embodiments, identifying the subject's suitability for NF treatment at block 104 includes identifying the subject as female. Alternatively or additionally, identifying the subject's suitability for NF treatment includes identifying the subject's PTSD condition as resulting from a non-civilian trauma event.

[0159] According to some exemplary embodiments, NF treatment is administered to the subject at block 106. In some embodiments, the NF treatment is administered for several consecutive weeks. In some embodiments, the NF treatment is administered for at least 8 consecutive weeks, e.g., at least 10 consecutive weeks, at least 12 consecutive weeks, at least 15 consecutive weeks, or any intermediate, shorter, or longer period thereof. In some embodiments, the NF treatment is administered for a period of 8 to 12 consecutive weeks, e.g., 8 to 9 consecutive weeks, 8 to 10 consecutive weeks, 9 to 11 consecutive weeks, or any intermediate, shorter, or longer period thereof.

[0160] According to some exemplary embodiments, the subject achieves a reduction in CAPS-5 score after NF treatment at block 108. In some embodiments, the subject achieves a reduction of at least 6 points, e.g., at least 6 points, at least 10 points, at least 15 points, or any intermediate, lesser, or greater reduction compared to the CAPS-5 score measured before NF treatment. In some embodiments, the subject achieves at least a 6-point reduction on the CAPS-5 scale after 8 to 12 weeks of NF treatment, optionally with a final treatment session occurring in the last week.

[0161] Exemplary Treatment Session

[0162] According to some exemplary embodiments, NF therapy for treating PTSD includes multiple therapy sessions. In some embodiments, the therapy sessions are conducted for at least 8 consecutive weeks. In some embodiments, the therapy sessions are conducted for a total of 8 to 12 weeks, e.g., 8 to 12 consecutive weeks. In some embodiments, the NF therapy includes at least 15 therapy sessions conducted over an 8 to 12 week period. In some embodiments, at least two therapy sessions are conducted every week or most weeks.

[0163] According to some exemplary embodiments of the present invention, as shown in FIG. 2, a treatment session of NF therapy for treating a subject diagnosed with PTSD is shown.

[0164] According to some exemplary embodiments, one or more electrodes are placed on the patient's head at block 230. In some embodiments, the one or more electrodes include multiple electrodes placed at different locations on the subject's head, for example, at C3, C4, Cz, FCZ, P3, Pz, P4 locations in a 10-20 coordinate system, or any combination of these locations. In some embodiments, the electrodes are attached to the patient's head (e.g., skull) using gel.

[0165] According to some exemplary embodiments, recording from the electrodes begins at block 232. In some embodiments, the electrodes are used to record EEG signals. In some embodiments, this recording begins at block 232 before or after electrode placement at block 230.

[0166] According to some exemplary embodiments, contact between the electrodes and the subject's head is determined in block 234. In some embodiments, this contact is determined based on the recording started in block 232. In some embodiments, the contact between the electrodes and the patient's head is presented to the supervisor using an interface that indicates which electrodes are in proper contact and which are not in proper contact. In some embodiments, the system alerts the supervisor and / or user which electrodes are not in proper contact during treatment and optionally indicates actions to take to resolve the issues. In some embodiments, after electrode contact is determined in block 234, recording is started in block 232.

[0167] According to some exemplary embodiments, the treatment session optionally includes an eyes-closed session at block 236. In some embodiments, during the eyes-closed session, signals are recorded while the patient is in rest mode and used, for example, to calibrate the recording and / or EEG measurement system.

[0168] According to some exemplary embodiments, the treatment session optionally includes a global baseline session at block 238. In some embodiments, during the global baseline session, EEG signals are measured and collected for a pre-determined period of time necessary to determine activity of at least one limbic brain region or a biomarker of that activity, e.g., using EFPs of the limbic brain region. In some embodiments, the pre-determined period is up to 3 minutes, e.g., up to 2.5 minutes, up to 2 minutes, up to 1.5 minutes, or up to 1 minute.

[0169] Optionally, a local baseline is calculated before each NF cycle. In some embodiments, during the local baseline session, EEG signals are measured and collected for a predetermined period of time necessary to determine the activity of at least one limbic brain region, for example, using EFP of the limbic brain region. In some embodiments, the predetermined period is less than 2 minutes, for example, less than 1.5 minutes, less than 1 minute, or an intermediate, smaller, or larger value.

[0170] According to some exemplary embodiments, the treatment session includes one or more training cycles at block 240. In some embodiments, the one or more training cycles include 1, 2, 3, 4, 5, 6, 7, or more NF training cycles. In some embodiments, the training cycles (e.g., NF training cycles) are consecutive training cycles. Optionally, the NF training cycles are performed consecutively at block 240. Optionally, the delay between two consecutive NF training cycles is less than 2 minutes, e.g., less than 60 seconds, less than 30 seconds, less than 10 seconds, less than 5 seconds, less than 1 second, or an intermediate, shorter, or longer period. Optionally, the training cycle includes at least one transfer cycle 242, in which feedback regarding the activation level of at least one limbic brain region was not provided to the patient.

[0171] According to some exemplary embodiments, during an NF cycle, a patient performs a task (e.g., a cognitive task and / or an affective task) while viewing a patient interface (e.g., a visual, audio, tactile, and / or olfactory interface) that presents scenarios that change depending on the determined activity level of at least one limbic brain region. In some embodiments, the cognitive task is selected to increase the activity level of at least one limbic brain region or a biomarker thereof. In some embodiments, an increase in activity of at least one limbic brain region or a biomarker thereof increases or decreases the amount of stimulation cues provided to the patient as part of the interface. Furthermore, visual, audio, tactile, and / or olfactory human-detectable notifications provided to the subject while viewing the interface indicate whether a target activity level or biomarker thereof in the limbic brain region has been exceeded or whether the determined activity is in a desired direction toward the target activity level.

[0172] Exemplary System for Administration of NF Treatment

[0173] According to some exemplary embodiments of the present invention, as shown in FIG. 3, a system for administration of NF therapy is shown.

[0174] According to some exemplary embodiments, the system 302 includes a control unit 304, a patient interface 306, and optionally, a supervisor interface 308. In some embodiments, the patient interface 306 and the supervisor interface are operatively connected to a control circuit 310 of the control unit 304. In some embodiments, the control unit 304 further includes a memory 312 that stores at least one algorithm and / or lookup table for use in determining the activity level of at least one limbic brain region. Alternatively or additionally, the memory 312 includes at least one EFP (e.g., an EFP model of at least one limbic brain region), such as the EFP models described in International Patent Application Publication No. WO2012104853A2, filed February 2, 2012, and International Patent Application Publication No. WO2020121299A1, filed December 9, 2019, the contents of which are incorporated by reference in their entireties. In some embodiments, the EFP model includes an EFP model of the amygdala. In some embodiments, the EFP model is applied to at least one EEG signal measured from electrodes on the subject's head and used to determine amygdala activity. In some embodiments, the memory stores at least one NF treatment protocol or multiple NF treatment protocols.

[0175] According to some exemplary embodiments, the control unit 304 includes an EEG recording unit 314 operatively connected to the control circuitry 310. In some embodiments, the EEG recording unit 314 transmits signals from one or more electrodes placed on the subject's head to the control circuitry 310, processes the received signals, and analyzes the processed signals to determine an activity level of at least one limbic brain region and / or a relationship between the determined activity and at least one reference value or indicator thereof stored in memory 312. In some embodiments, the control circuitry 310 determines the activity level or a relationship between the activity level and at least one reference value or indicator thereof using at least one algorithm, lookup table, and EFP stored in memory 312, as described, for example, in International Patent Application Publication No. WO2012104853A2 filed February 2, 2012, and International Patent Application Publication No. WO2020121299A1 filed December 9, 2019, the contents of which are incorporated by reference in their entireties.

[0176] According to some exemplary embodiments, the EEG recording unit is operatively coupled to at least one electrode, e.g., a plurality of electrodes 316 and 318, disposed on the head 320 of the patient 322. In some embodiments, the plurality of electrodes includes two, three, four, five, six, seven, eight, nine, ten, or more electrodes disposed on and optionally attached to the head 320 of the patient 322. Optionally, the plurality of electrodes is arranged in an array. In some embodiments, the electrodes are positioned at specific locations on the subject's head, e.g., C3, C4, Cz, FCz, P3, Pz, P4, or any combination of these locations, in an extended 10-20 coordinate system. Alternatively, the electrodes are positioned at any location or combination of locations in the extended 10-20 coordinate system. In some embodiments, the control unit 304 is connectable to at least one speaker or earphone 324 configured to transmit audio signals to the patient 322.

[0177] According to some exemplary embodiments, the control unit includes a communications circuit 326 configured to receive and / or transmit signals, for example, to transmit wireless signals to a remote device (e.g., a remote computer, a remote server, a remote cloud, a remote storage cloud, a remote processing cloud) located outside the supervising clinic. In some embodiments, the remote device stores at least one algorithm, a lookup table, and / or an EFP. In some embodiments, the remote device stores a plurality of NF treatment protocols. In some embodiments, the control unit 304 transmits electrical signals or processed electrical signals to the remote device via the communications circuit 326 and receives signals via the communications circuit 326 indicative of activity levels in limbic brain regions and / or a relationship between activity levels in limbic brain regions and baseline values ​​indicative of target activation levels in limbic brain regions.

[0178] According to some exemplary embodiments, the control circuitry 310 signals the patient interface 306 to display a visual and / or audio interface and / or tactile and / or olfactory cues on a screen that continuously change in response to activation levels or changes in activation levels relative to baseline of limbic brain regions or their biomarkers. In some embodiments, the interface is updated based on signals received from the electrodes (e.g., electrodes 316 and 318) every 0.5 seconds, 1 second, 5 seconds, 10 seconds, 15 seconds, 20 seconds, 25 seconds, or any intermediate, smaller, or larger value. In some embodiments, the patient interface 306 changes the visual interface presented to the patient with a delay of about 5 seconds, about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, or any intermediate, smaller, or larger value relative to when electrical signals are received from the electrodes 316 and 318. In some embodiments, the patient interface includes a display and / or a speaker.

[0179] According to some exemplary embodiments, the patient interface, e.g., a visual interface, is provided in two dimensions (2D) or three dimensions (3D). In some embodiments, the patient interface is provided using virtual reality, augmented reality, with or without at least one of audio, olfactory, and tactile feedback.

[0180] According to some exemplary embodiments, the control circuitry 310 signals the supervisor interface to provide visual and / or audio notifications to the treatment supervisor. In some embodiments, the visual and / or audio notifications indicate at least one of the patient's progress during treatment, activity levels of limbic brain regions (e.g., the amygdala) or biomarkers thereof, changes in limbic brain region activity levels, differences between baseline and limbic brain region activity levels, the stage of the NF session, the operation of the system, and notifications or cues provided to the patient. Optionally, the supervisor interface 308 is a remote supervisor device connected to the control unit 304 via the communications circuitry 326. In some embodiments, the control unit 304 transmits at least one of data collected from the patient, data transmitted to the supervisor, or data displayed to the supervisor to the remote device, for example, to generate a database. In some embodiments, the dataset includes information collected from multiple systems and / or multiple patients.

[0181] According to some exemplary embodiments, at least one of the patient interface 306, the electrodes 316 and 318, and the supervisor interface 308 are in communication with the communication circuitry 326, for example, using wireless communications and signals.

[0182] According to some exemplary embodiments, control circuitry 310 is configured to administer NF treatment to the PTSD patient based on at least one protocol or notification of the protocol stored in memory 312. Additionally, control circuitry 310 is configured to signal at least a user interface (e.g., supervisor interface 318) to generate a notification with information for evaluating the results of the NF treatment between 8 and 12 weeks after initiating administration of the NF treatment.

[0183] According to some exemplary embodiments, the control circuitry 310 is configured to receive an input signal including information regarding the evaluation results, send a signal to at least one user interface, and generate a notification with information including a suggestion to modify at least one NF treatment protocol or to discontinue administration of the NF treatment based on the evaluation results.

[0184] According to some exemplary embodiments, memory 312 stores a plurality of protocols for NF treatment. In some embodiments, control circuitry 310 is configured to receive an input signal including information regarding the evaluation results, and to send a signal to at least one user interface to generate a notification with information including a suggestion to replace at least one protocol of NF treatment with a different protocol of the plurality of protocols based on the evaluation results.

[0185] According to some exemplary embodiments, the system includes at least one remote device that stores a plurality of protocols for NF treatment. In some embodiments, communications circuitry 326 is configured to communicate with the at least one remote device. In some embodiments, control circuitry 310 is configured to receive an input signal including information regarding the evaluation results, send a signal to at least one user interface, and generate a notification with information including a suggestion to replace at least one protocol for NF treatment with a different protocol from the plurality of protocols stored on the remote device based on the evaluation results.

[0186] According to some exemplary embodiments, the control circuitry 310 is configured to send a signal to the patient interface 306 to present an interface stored in the memory 312 to the patient 322 (e.g., a PTSD patient). Additionally, the control circuitry 310 is configured to measure EEG signals using electrical signals received by the EEG recording unit 314. In some embodiments, the control circuitry 310 detects changes in activity of the amygdala or at least one associated brain region using the measured EEG signals and at least one algorithm and / or electrical fingerprint (EFP) of the amygdala or at least one associated brain region stored in the memory 312. In some embodiments, the control circuitry 310 alters the presentation of the interface to the patient 322 in response to the detected change in activity.

[0187] Sample PTSD Assessment

[0188] Reference is now made to FIG. 4A, which illustrates an evaluation of NF treatment according to some exemplary embodiments of the present invention.

[0189] According to some exemplary embodiments, NF treatment is administered to a subject over a period of several weeks, as described in block 106 shown in FIG. 1. In some embodiments, NF treatment is administered for at least 8 consecutive weeks. In some embodiments, NF treatment is administered for a period of 8 to 12 consecutive weeks. In some embodiments, NF treatment is administered for a period of non-consecutive weeks.

[0190] According to some exemplary embodiments, an evaluation of the success of the NF treatment is performed at block 402, 8 to 12 weeks after the start of administration of the NF treatment. Optionally, this evaluation is performed during administration of the NF treatment. In some embodiments, this evaluation includes determining a change in score on one or more PTSD-related measures after the NF treatment compared to a baseline score on the measures before the start of the NF treatment. In some embodiments, the one or more relevant PTSD measures include at least one of the CAPS-5, PCL-5, Emotion Regulation Questionnaire (ERQ), Patient Health Questionnaire (PHQ-9), and Clinical Global Impression (CGI). Alternatively or additionally, this evaluation is performed by a medical professional without the use of the above measures.

[0191] According to some exemplary embodiments, NF treatment is discontinued at block 404. In some embodiments, NF treatment is discontinued based on the results of the assessment performed in block 404. In some embodiments, NF treatment is discontinued, for example, if the assessment indicates no improvement in the condition of the subject receiving NF treatment or if the subject's condition is worsening.

[0192] According to some exemplary embodiments, the NF treatment is modified at block 406. In some embodiments, at least one parameter of the NF treatment is modified at block 406 based on the evaluation results. In some embodiments, the at least one parameter includes at least one of the number of treatment sessions, the number of weeks of treatment, the length of each treatment session, the number of sessions per week, and the interval between two sessions. In some embodiments, the modified NF treatment is administered to the subject.

[0193] According to some exemplary embodiments, the subject is transitioned to a different treatment, e.g., a different psychotherapy, at block 408. In some embodiments, the subject is transitioned to a different treatment based on the results of the assessment. In some embodiments, the subject is transitioned to a different treatment, for example, if the assessment indicates no improvement in the subject's condition receiving the NF treatment or if the subject's condition is worsening. In some embodiments, the different psychotherapy includes at least one of psychotherapy, psychotherapy, and treatment with a bioactive agent (e.g., a drug).

[0194] According to some exemplary embodiments, the NF treatment is combined with an additional treatment at block 410. In some embodiments, the NF treatment is combined with the additional treatment based on the results of the assessment. In some embodiments, the additional treatment includes at least one of an additional NF treatment aimed at modulating the activity of a different brain region or its biomarkers, psychotherapy, psychotherapy, and treatment using a bioactive agent (e.g., a drug).

[0195] According to some exemplary embodiments, the NF treatment is continued at block 412. In some embodiments, the NF treatment provided at block 106 is continued based on the evaluation results. In some embodiments, if the NF treatment is continued, the NF treatment is continued if the evaluation results indicate a likelihood of successful achievement of one or more NF treatment goals.

[0196] Exemplary NF Treatments for Specific Subpopulations

[0197] According to some exemplary embodiments, NF treatment is administered to subjects in a specific subpopulation who are more suitable to receive NF treatment compared to the population at large.

[0198] Reference is now made to FIG. 4B, which illustrates the administration of NF treatment to a female subject diagnosed with PTSD, according to some exemplary embodiments of the present invention.

[0199] According to some exemplary embodiments, the female subject is diagnosed with PTSD at block 420, for example, as described in block 102 of FIG.

[0200] According to some exemplary embodiments, NF treatment is administered to the female subject for at least 8 weeks, e.g., at least 10 weeks, optionally for consecutive weeks, at block 422. In some embodiments, NF treatment is administered for a period of 4 to 12 consecutive weeks, e.g., a period of 8 to 12 consecutive weeks.

[0201] According to some exemplary embodiments, after NF treatment, at block 424, a reduction in the PTSD scale or equivalent indicator is achieved.

[0202] Reference is now made to FIG. 4C, which illustrates the administration of NF treatment to a subject diagnosed with PTSD resulting from a non-civilian trauma, according to some exemplary embodiments of the present invention.

[0203] According to some exemplary embodiments, a subject with PTSD resulting from a non-civilian trauma is diagnosed with PTSD at block 430, for example, as described in block 102 of FIG.

[0204] According to some exemplary embodiments, NF treatment is administered to the female subject for a continuous period of at least four weeks, e.g., at least eight weeks, at block 432. In some embodiments, NF treatment is administered for a continuous period of four to twelve weeks, e.g., for a continuous period of eight to twelve weeks.

[0205] According to some exemplary embodiments, after NF treatment, at block 434, a reduction in the PTSD scale is achieved.

[0206] Exemplary Systems and Methods for Evaluation of PTSD Treatments

[0207] According to some exemplary embodiments, the evaluation of the effectiveness of a PTSD treatment administered to a subject (e.g., a patient or group of patients) is performed by a device (e.g., an evaluation device). In some embodiments, the device receives information including the results of at least one assessment (e.g., cognitive, psychiatric, and / or functional assessment) administered to the subject after at least one week of NF treatment. In some embodiments, the information includes the results of a subject assessment administered to the subject after at least four weeks, at least eight weeks, or any shorter or longer period in between. In some embodiments, the information includes the results of a subject assessment administered to the subject after at least one NF treatment session or at least one week of NF treatment.

[0208] According to some exemplary embodiments, the information is used to determine whether a given NF treatment is progressing according to an expected improvement pathway or is not sufficiently effective for a particular subject or population. In some embodiments, if the system determines that a NF treatment administered to a patient or group of patients is not sufficiently effective, the system provides a notification with instructions (e.g., suggestions or recommendations) on how to modify the NF treatment, replace or combine it with a different treatment, or discontinue the NF treatment.

[0209] According to some exemplary embodiments, the evaluation is performed during the subject's NF treatment regimen, e.g., to improve the effectiveness of the NF treatment or overall treatment for the subject. Alternatively or additionally, the evaluation is performed to administer a more effective treatment to at least one new subject beginning a new treatment regimen.

[0210] According to some exemplary embodiments, the evaluation identifies at least one subpopulation within the larger subject population for which a NF treatment is less or more effective, allowing for modification of the NF treatment or the overall treatment administered to subjects belonging to the at least one subpopulation, and optionally increasing the effectiveness of the treatment administered to the subjects.

[0211] According to some exemplary embodiments, the evaluation allows for the definition of at least one new subpopulation or subpopulations that exhibit a response that differs from the response of other identified subpopulations and / or larger subpopulations.

[0212] Reference is now made to FIG. 5C, which illustrates a device for assessing the effectiveness of NF treatment, according to some exemplary embodiments of the present invention.

[0213] According to some exemplary embodiments, device 520 (e.g., evaluation device) is a standalone device used to monitor NF PTSD treatment and / or manage PTSD patients. Alternatively or additionally, the evaluation device is a component of a device or system for administering NF treatment. In some embodiments, the NF treatment is a patient-controlled NF treatment, for example, reducing activity in a limbic brain region or limbic network (e.g., reducing activity in the amygdala). In some embodiments, the NF treatment is based solely on recording EEG signals and a model (e.g., fingerprint) used to interpret the recorded EEG signals into an index of activity or modulation of at least one of a limbic brain region, a limbic network, and / or the amygdala.

[0214] According to some exemplary embodiments, device 520 is a server, cloud storage and / or processing, or any remote device that communicates directly or indirectly with a patient and / or a professional (e.g., a therapist, physician, or medical professional administering and / or monitoring NF treatment).

[0215] According to some exemplary embodiments, the device includes control circuitry 522 (e.g., a controller) and memory circuitry (e.g., memory 524). In some embodiments, memory 524 stores information for at least one patient, e.g., a patient diagnosed with a stress disorder (e.g., PTSD). Alternatively or additionally, memory 524 stores information including the results of, or an indicator of, at least one patient assessment conducted at least one session after initiating administration of NF treatment to the patient or group of patients, or at least one week after, e.g., at least four weeks after, at least eight weeks after, or any intermediate, shorter, or longer period of time.

[0216] According to some exemplary embodiments, the outcome is a patient assessment using at least one rating scale, e.g., the CAPS-5 scale, the CGI scale, the PCL-5 scale, the ERQ scale, and / or the PHQ-9 scale. In some embodiments, the outcome includes at least one convergence measure of the outcome (e.g., the mean, median, and mode of the assessment outcome).

[0217] Additionally, memory 524 includes at least one predicted measure of the assessment or an indicator thereof. In some embodiments, the predicted result is in the form of a formula, model, or algorithm. Optionally, the predicted measure includes a concentration tendency measure of the predicted measure. In some embodiments, the predicted measure is based on the assessment results shown in Table A and / or at least one of the graphs shown in Figures 6A-6F, 7A-7F, 8A-8B, and 9A-9B.

[0218] According to some exemplary embodiments, memory 524 stores one or more algorithms, formulas, models, and / or lookup tables for processing and / or analyzing patient assessment results and predicted outcomes, and optionally for determining relationships between the assessment results and predicted outcomes. In some embodiments, the one or more algorithms, formulas, models, and / or lookup tables stored in this memory are used to generate at least one notification (optionally with instructions to a user or professional) based on at least one of the assessment results, predicted outcomes, and / or determined relationships.

[0219] According to some exemplary embodiments, the control circuitry 522 is configured to at least one of process the received assessment results, process the stored expected results, determine a relationship between the received assessment results and the expected results, and determine that the received assessment results are lower than the expected results, and to generate at least one notification based on the determined relationship using any content (e.g., any information) stored in the memory 524.

[0220] According to some exemplary embodiments, control circuitry 522 is configured to generate at least one notification (e.g., a human-detectable notification). In some embodiments, the control circuitry generates the notification based on the results of processing the assessment results and / or the processing of the predicted results, and / or based on a determined relationship between the assessment results and the predicted results. In some embodiments, the notification includes one or more instructions stored in memory 524.

[0221] According to some demonstrative embodiments, device 520 includes communications circuitry 526. In some embodiments, communications circuitry 526 is configured to receive and / or transmit signals, for example, wireless signals (e.g., wireless communications signals, Wi-Fi signals, Bluetooth signals, IR signals, optical signals, or other types of signals used for wireless communications). In some embodiments, device 520 receives information stored in memory 524 from a remote device (e.g., a device located more than one meter away from device 520 or any device in communication with device 520) via communications circuitry 526. In some embodiments, device 520 transmits information and / or at least one notification generated by control circuitry 522 to the remote device via communications circuitry.

[0222] According to some exemplary embodiments, device 520 optionally includes a user interface 528. In some embodiments, user interface 528 is used to receive input and / or provide at least one notification to a user of device 520.

[0223] Reference is now made to FIG. 5D, which illustrates a general process for assessing the effect of NF treatment on a subject, performed by a device (e.g., device 520) according to some exemplary embodiments of the present invention.

[0224] According to some exemplary embodiments, a device, e.g., a device for assessing the effectiveness of NF treatment, receives information regarding the effectiveness of NF treatment for at least one subject (e.g., a patient). In some embodiments, the information includes results of an assessment conducted before treatment and / or after initiation of NF treatment, e.g., at least one week (e.g., at least four weeks, at least eight weeks) after initiation of administration of NF treatment to the patient. In some embodiments, the information includes results of an assessment conducted after at least one NF treatment session. In some embodiments, the assessment results include scores on a rating scale (e.g., the CAPS-5 scale, the CGI scale, the PCL-5 scale, the ERQ scale, and / or the PHQ-9 scale). In some embodiments, the received information is stored in a memory of the device (e.g., memory 524 shown in FIG. 5C ).

[0225] According to some exemplary embodiments, the device, e.g., the device's control circuitry, determines whether the effect of the NF treatment is a desired effect (e.g., a target effect) at block 532. In some embodiments, the control circuitry (e.g., control circuitry 522) uses at least one of an algorithm, a formula, a model, and / or a look-up table stored in memory 524 for this determination. For example, the determination of treatment effect is made by determining a relationship between the evaluation results and the expected outcome stored in memory 524. In some embodiments, determining the relationship includes comparing the evaluation results or an indicator thereof to the expected outcome or an indicator thereof. Optionally, determining the relationship includes determining a relationship between a convergence tendency measure of the evaluation results and a convergence tendency measure of the expected outcome.

[0226] According to some exemplary embodiments, the device generates at least one notification at block 534. In some embodiments, device 520 (e.g., control circuitry 522) generates at least one notification based on the determination, e.g., if the effect is a desired effect and / or if the effect is not a desired effect. In some embodiments, control circuitry 522 generates a notification if the evaluation result is lower than the expected result, optionally indicating that the effect of the NF treatment on the subject or group of subjects is lower or higher than the expected effect. In some embodiments, the expected effect is the effect of the NF treatment measured in a population of subjects after a specified period of time after initiating the NF treatment.

[0227] According to some exemplary embodiments, the notification is a human-detectable notification, e.g., an audio and / or visual notification. In some embodiments, the notification includes instructions to a professional monitoring the NF treatment administered to the subject, including how to modify the NF treatment or the overall treatment provided to the subject in light of the evaluation results. For example, the notification includes instructions to discontinue the NF treatment, modify at least one parameter of the NF treatment, replace the NF treatment protocol with a different treatment protocol, and / or replace or combine the NF treatment with at least one additional treatment or discontinue or modify other treatments.

[0228] According to some example embodiments, the notification is optionally provided to the remote device at block 536. In some embodiments, the notification is provided to the remote device by device 520 using communications circuitry 526.

[0229] Alternatively or additionally, the notification and / or information stored in memory 524 is used to improve at least one existing NF treatment protocol, which in some embodiments is stored in memory 524 of device 520, or in a memory of a remote device (e.g., a server, cloud storage), or in a database within the remote device.

[0230] Reference is now made to FIG. 5E, which illustrates a detailed evaluation process according to some exemplary embodiments of the present invention.

[0231] According to some exemplary embodiments, an assessment device, e.g., device 520 shown in FIG. 5C , receives, in block 538, results of a subject assessment conducted after initiating NF treatment, e.g., at least one week after initiating NF treatment or after at least one session of NF treatment. In some embodiments, in block 538, the results are results of a subject assessment conducted at least eight weeks after initiating NF treatment. In some embodiments, the results include results from at least one of the CAPS-5 rating scale, CGI rating scale, PCL-5 rating scale, ERQ rating scale, and / or PHQ-9 rating scale. In some embodiments, a subject, e.g., a patient diagnosed with a stress disorder (e.g., PTSD), is assessed at least eight weeks after initiating NF treatment. Optionally, the subject is assessed at the end of the planned NF treatment, e.g., after completing the last NF treatment session or at least one day after completing NF treatment or the last NF treatment session.

[0232] According to some exemplary embodiments, the assessment results are received from a remote device via a communications circuit (e.g., communications circuit 526 shown in FIG. 5C). Alternatively or additionally, the assessment results are received via a user interface (e.g., user interface 528) of the device.

[0233] According to some exemplary embodiments, the assessment results are the results of at least one assessment performed on a patient or group of patients.

[0234] According to some exemplary embodiments, the relationship between the assessment results, e.g., the received assessment results, and the expected results is determined at block 540. In some embodiments, the expected results or indicators thereof are stored in the memory of the device in the form of at least one central tendency, formula, model, algorithm, or look-up table of the expected results. In some embodiments, the expected results are the results of at least one assessment measured after a specified period of time similar to the period during which the received assessment results were measured in a subject in which NF treatment has had a desired effect (e.g., a target effect) in that subject.

[0235] According to some exemplary embodiments, the device determines that the received assessment results are lower than expected results at block 542. In some embodiments, determining that the received assessment results are lower than expected results indicates that the effect of the NF treatment on the subject is less than the targeted, desired effect of the NF treatment or greater than expected effect.

[0236] Alternatively, the device determines that the received assessment result is higher than the expected result, indicating that the effect of the NF treatment is greater than expected.

[0237] According to some exemplary embodiments, where the assessment consists of the CAPS-5, the expected outcome includes at least a 6-point reduction on the CAPS-5 scale after at least 4 weeks, e.g., after at least 4 weeks of NF treatment or after completing at least 50% of the planned NF treatment sessions.

[0238] According to some exemplary embodiments, if the assessment consists of a PCL-5, the expected outcome includes a reduction of at least 9 points on the PCL-5 scale after at least 4 weeks, e.g., after at least 8 weeks of NF treatment, or after completing at least 50% of the planned NF treatment sessions.

[0239] According to some exemplary embodiments, the device generates at least one notification at block 544. In some embodiments, the device 520, e.g., the control circuitry 522, generates the notification based on the determined relationship or based on determining that the assessment result is lower or higher than the expected result. In some embodiments, the notification includes instructions on how to approve the treatment (e.g., NF treatment or a combination of NF treatment and at least one additional treatment) administered to the patient to enhance the effectiveness of the NF treatment for the subject. In some embodiments, the assessment results measure the patient's condition (e.g., the patient's clinical, mental, cognitive, and / or functional status) after and optionally during the NF treatment. In some embodiments, the notification includes instructions on how to improve the subject's condition.

[0240] According to some exemplary embodiments, the instructions include instructions to modify at least one parameter of an existing NF treatment provided to the patient and, optionally, administer at least one NF treatment session to the patient using the modified parameters, in some embodiments, the at least one parameter includes at least one of a duration of the NF treatment session, a number of additional NF treatment sessions, a type and / or content of a visual interface presented to the patient during the NF treatment session, and an analysis performed on EEG signals recorded from the subject's brain during the NF treatment session.

[0241] According to some exemplary embodiments, the instructions include instructions to replace an existing NF treatment protocol with a different protocol and, optionally, administer at least one treatment session to the patient using the different protocol.

[0242] According to some exemplary embodiments, the instructions include instructions to discontinue (optionally temporarily) the NF treatment administered to the subject, or, alternatively, the instructions include instructions to administer at least one additional NF treatment session to the patient using an existing NF treatment protocol.

[0243] According to some exemplary embodiments, the instructions include replacing the NF treatment with at least one different treatment. Alternatively, the instructions include combining the NF treatment using an existing or different treatment protocol with at least one different treatment. In some embodiments, the at least one different treatment includes at least one of cognitive behavioral therapy (CBT), psychotherapy, psychotherapy, and / or pharmacotherapy.

[0244] According to some exemplary embodiments, if the received assessment results indicate that the effect of the NF treatment is greater than expected, the generated notification includes instructions to modify the NF treatment or the overall treatment administered to the subject, for example, to shorten the NF treatment, to shorten an NF treatment session, to increase the difficulty of at least one element of an NF treatment session, to increase the time between NF treatment sessions, and / or to discontinue the NF treatment.

[0245] According to some demonstrative embodiments, the generated notification is provided at block 546. In some embodiments, providing the generated notification includes providing the notification to a remote device (e.g., a remote computer) using communications circuitry 526.

[0246] According to some exemplary embodiments, the received results include assessment results for a large patient population (e.g., a population of at least 10 patients). In some embodiments, the device is configured to process the received results by, for example, sorting or categorizing the received results according to patients from a particular subpopulation who underwent the assessment (e.g., a population of female subjects, a population of male subjects, a population of subjects whose PTSD is due to civilian trauma, and a population of subjects whose PTSD is due to non-civilian trauma).

[0247] According to some exemplary embodiments, the device uses the classified results of the subpopulations to determine the effectiveness of the NF treatment for a particular subpopulation and alters the treatment provided to the subpopulation if the effect of the NF treatment for this subpopulation is less than the expected target effect.

[0248] Reference is now made to FIG. 5F, which illustrates a process for determining the effectiveness of NF treatment for specific patient subpopulations, according to some exemplary embodiments of the present invention.

[0249] According to some exemplary embodiments, the assessment results received at block 538 include assessment results from a group of patients. In some embodiments, each patient had at least one assessment after initiating NF treatment, e.g., after at least four weeks of NF treatment.

[0250] According to some exemplary embodiments, the device processes the received results to isolate results for at least one particular patient subpopulation at block 548. In some embodiments, this processing includes sorting or classifying the overall results to isolate results for at least one particular subpopulation. In some embodiments, this processing further includes calculating central tendency of the isolated results.

[0251] According to some exemplary embodiments, the device determines that the isolated outcome or its central tendency is lower or higher than the expected outcome at block 550. In some embodiments, the device determines the relationship between the isolated outcome and the expected outcome to determine that the isolated outcome is lower than the expected outcome. In some embodiments, the expected outcome is a result of at least one assessment in patients of a subpopulation that is indicative of a desired effect (e.g., a target effect) of NF treatment for patients associated with the subpopulation.

[0252] According to some exemplary embodiments, a notification is generated at block 552. In some embodiments, the notification is based on a determined relationship between the subpopulation outcome and the expected outcome. Alternatively, the notification is generated in response to determining that the subpopulation outcome is lower than the expected outcome. In some embodiments, the generated notification includes instructions to modify the NF treatment administered to patients belonging to at least one subpopulation, for example, as described in block 544 of FIG. 5E.

[0253] According to some example embodiments, this notification is provided at block 554, for example, as described in block 546 of FIG. 5E.

[0254] According to some exemplary embodiments, processing the received assessment results to identify and isolate outcomes for specific subpopulations occurs after determining that the assessment results for a larger population are lower than expected, indicating that the NF treatment will have a less-than-targeted effect for the larger population. In some embodiments, the processing is performed to identify at least one specific subpopulation for which the NF treatment will have a lower-than-expected effect, and to administer a more tailored NF treatment to this specific subpopulation.

[0255] In some embodiments of the present invention, some or all of the methods described in Figures 5D-5F are optionally performed by a device different from the device described in Figure 5C.

[0256] Exemplary Clinical Trials

[0257] Clinical trials

[0258] A clinical trial was conducted to evaluate the clinical efficacy of NF treatment on a population of human subjects diagnosed with PTSD (e.g., chronic PTSD).

[0259] Reference is now made to Figure 5A, which shows a flowchart of the study protocol. In block 502, subjects are screened, e.g., to select a subject population for the study. In this clinical trial, and in some embodiments of the present invention, the subject population is comprised of subjects who meet the following eligibility criteria: subjects between 22 and 65 years of age; subjects diagnosed with PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V); and subjects who have been present for 1 to 20 years since the traumatic event. Furthermore, the subject population for this clinical trial is comprised of the following additional eligibility criteria: subjects of any gender; subjects who are able to sign informed consent; subjects with normal or corrected-to-normal vision; subjects with normal or corrected-to-normal hearing; and subjects who are able to comply with the study schedule.

[0260] During screening in Block 502, participants who agree to participate in the study and sign an informed consent form will be screened according to eligibility criteria and their diagnoses confirmed using the International Neuropsychiatric Interview (MINI for DSM-V).

[0261] Baseline assessments of clinical outcome measures were recorded in block 504. Additionally, during the baseline assessment or in conjunction with the first NF treatment (e.g., EEG-NF treatment), subjects underwent a roughly 10-minute "pre-training" session to familiarize themselves with the system prior to the actual EEG-NF treatment session.

[0262] At block 506, NF treatment, also referred to herein as NF training, was administered. Each subject in this study completed a total of 15 treatment sessions (also referred to herein as training sessions), two days per week on non-consecutive days, for a total treatment period (also referred to herein as training period) of eight consecutive weeks. The first training session occurred within seven days of the baseline assessment at block 504. In this study, and in some embodiments of the present invention, each training session lasted approximately 30 minutes, including EEG electrode placement, signal quality testing, and EEG-NF training (net time for the neurofeedback training itself was approximately 25 minutes per session).

[0263] Figure 5B illustrates the use of EFP in a system neurofeedback paradigm in this study and in some embodiments of the present invention. Recorded EEG data (1) are cleaned and transformed (2) as described above, then multiplied (3) by coefficients of the EFP model's time delay × frequency × weighting matrix to generate EFP values ​​(4). Changes in EFP values ​​(relative to a local baseline) are reflected as changes in an animated audiovisual interface.

[0264] Post-training assessments were performed at block 508. In this study, and in some embodiments of the present invention, the first follow-up assessment was performed immediately after the last EEG-NF training session or within 7 days (8-9 weeks) thereafter. All clinical outcome measures were assessed.

[0265] A three-month follow-up assessment was conducted at block 510. In this study, and in some embodiments of the present invention, a second follow-up assessment was conducted three months after completion of the final EEG-NF training session. All clinical outcome measures were measured.

[0266] Each subject participated in the study for a total of approximately 5 months (22 weeks) from the Screening Visit to the final (3-month) Follow-up Assessment Visit.

[0267] During the study, different assessment tools (e.g., rating scales) were used to assess the status of study participants after NF training compared to baseline measurements. In some embodiments of the present invention, one or more rating scales are used. These include the CAPS-5, Clinical Global Impression (CGI) scale, PTSD Checklist Adapted for DSM-5 (PCL-5), Emotion Regulation Questionnaire (ERQ), and Patient Health Questionnaire (PHQ-9).

[0268] Clinical trial results

[0269] In this clinical trial, and in some embodiments of the present invention, the status of subjects (e.g., PTSD patients) receiving NF treatment is evaluated post-treatment, e.g., after 8-12 weeks of NF treatment and / or 3 months after completion of NF treatment.

[0270] Table A below summarizes the change in scores on the different measures after 8 weeks of NF training (compared to baseline scores) in the overall population and in different subpopulations.

[0271] [Table 1]

[0272] As shown in Table A, in this clinical trial, the overall patient population achieved a mean reduction of 11.8 points on the CAPS-5 scale, a mean reduction of 9.6 points on the PCL-5 scale, and a mean reduction of 2.9 points on the PHQ-9 scale compared to baseline measurements after 8 weeks of NF treatment.

[0273] As shown in Table A, in this clinical trial, a subpopulation of female patients achieved a mean reduction of 15.3 points on the CAPS-5 scale, a mean reduction of 14.6 points on the PCL-5 scale, and a mean reduction of 4.6 points on the PHQ-9 scale compared to baseline measurements after 8 weeks of NF treatment.

[0274] As shown in Table A, in this clinical trial, a subpopulation of male patients achieved a mean reduction of 8.6 points on the CAPS-5 scale, a mean reduction of 4.8 points on the PCL-5 scale, and a mean reduction of 1.3 points on the PHQ-9 scale compared to baseline measurements after 8 weeks of NF treatment.

[0275] As shown in Table A, in this clinical trial, the subpopulation of patients diagnosed with PTSD resulting from non-civilian trauma achieved a mean reduction of 7.4 points on the CAPS-5 scale, a mean reduction of 3.9 points on the PCL-5 scale, and a mean reduction of 1.2 points on the PHQ-9 scale compared to baseline measurements after 8 weeks of NF treatment.

[0276] As shown in Table A , in this clinical trial, the subpopulation of patients diagnosed with PTSD resulting from civilian trauma (versus non-civilian trauma) achieved a mean reduction of 15.3 points on the CAPS-5 scale, a mean reduction of 14 points on the PCL-5 scale, and a mean reduction of 4.2 points on the PHQ-9 scale compared to baseline measurements after 8 weeks of NF treatment.

[0277] Table B below summarizes the change in scores on the different scales at the 3-month follow-up assessment (compared to baseline scores) for the overall population and different subpopulations.

[0278] [Table 2]

[0279] As shown in Table B, in this clinical trial, the overall patient population achieved a mean reduction of 13.5 points on the CAPS-5 scale, a mean reduction of 12.9 points on the PCL-5 scale, and a mean reduction of 4 points on the PHQ-9 scale 3 months after completing NF treatment (3-month follow-up) compared to baseline measurements.

[0280] As shown in Table B, in this clinical trial, a subpopulation of female patients achieved a mean reduction of 17.6 points on the CAPS-5 scale, a mean reduction of 16.6 points on the PCL-5 scale, and a mean reduction of 5.3 points on the PHQ-9 scale 3 months after completing NF treatment (3-month follow-up) compared to baseline measurements.

[0281] As shown in Table B, in this clinical trial, a subpopulation of male patients achieved a mean reduction of 9.6 points on the CAPS-5 scale, a mean reduction of 9.3 points on the PCL-5 scale, and a mean reduction of 2.7 points on the PHQ-9 scale 3 months after completing NF treatment (3-month follow-up) compared to baseline measurements.

[0282] As shown in Table B, in this clinical trial, the subpopulation of patients diagnosed with PTSD resulting from non-civilian trauma achieved a mean reduction of 7.6 points on the CAPS-5 scale, a mean reduction of 7.2 points on the PCL-5 scale, and a mean reduction of 2.7 points on the PHQ-9 scale 3 months after completing NF treatment (3-month follow-up) compared to baseline measurements.

[0283] As shown in Table B, in this clinical trial, the subpopulation of patients diagnosed with PTSD resulting from civilian trauma achieved a mean reduction of 17.9 points on the CAPS-5 scale, a mean reduction of 17.1 points on the PCL-5 scale, and a mean reduction of 4.9 points on the PHQ-9 scale 3 months after completing NF treatment (3-month follow-up) compared to baseline measurements.

[0284] Figure 6A shows boxplots depicting the distribution of CAPS-5 scores for the study population at three time points: (1) baseline, (2) after 8 weeks of treatment, and (3) 3 months after the last NF session (i.e., 5 months after treatment initiation).

[0285] As can be seen from the figure, the mean CAPS-5 score decreased from 40 points to 26.8 points after 8 weeks of NF training.

[0286] Figure 6B shows box plots showing the distribution of CAPS-5 (Re-experiencing) Cluster B scores for the study population at three time points and decline over time.

[0287] FIG. 6C shows box plots showing the distribution of CAPS-5 (Avoidance) Cluster C scores for the population in the study at three time points and decline over time.

[0288] FIG. 6D shows a boxplot showing the distribution of CAPS-5 (negative changes in mood) Cluster D scores for the study population at three time points and decline over time.

[0289] Figure 6E shows a boxplot showing the distribution of CAPS-5 (Altered Alertness and Responsiveness) Cluster E scores for the study population at three time points and decline over time.

[0290] Figure 6F shows a boxplot showing the distribution of CAPS-5 (impairing psychological disturbances) Cluster G scores for the study population at three time points and decline over time.

[0291] Figure 7A shows a boxplot showing the distribution of CAPS-5 scores at three time points and decline over time for the civilian trauma population in the study.

[0292] Figure 7B shows boxplots depicting the distribution of CAPS-5 (reexperiencing) Cluster B scores at three time points and decline over time for the civilian trauma population in the study.

[0293] Figure 7C shows boxplots illustrating the distribution of CAPS-5 (Avoidance) Cluster C scores at three time points and decline over time for the civilian trauma population in the study.

[0294] Figure 7D shows a boxplot showing the distribution of CAPS-5 (negative changes in mood) Cluster D scores at three time points and decline over time for the civilian trauma population in the study.

[0295] Figure 7E shows a boxplot illustrating the distribution of Cluster E scores on the CAPS-5 (Altered Arousal and Reactivity) at three time points and decline over time for the civilian trauma population in the study.

[0296] Figure 7F shows a boxplot showing the distribution of CAPS-5 (psychological disturbances causing impairment) Cluster G scores at three time points and decline over time for the civilian trauma population in the study.

[0297] Figure 8A shows boxplots depicting the distribution of PCL-5 scores for the study population at three time points: (1) baseline, (2) after 8 weeks of treatment, and (3) 3 months after the last NF session (i.e., 5 months after treatment initiation).

[0298] Figure 8B shows box plots showing the distribution of PCL-5 scores at three time points and decline over time for the civilian trauma population in the study.

[0299] Figure 9A shows boxplots depicting the distribution of PHQ-9 scores for the study population at three time points: (1) baseline, (2) after 8 weeks of treatment, and (3) 3 months after the last NF session (i.e., 5 months after treatment initiation).

[0300] Figure 9B shows a boxplot showing the distribution of PHQ-9 scores at three time points and decline over time for the civilian trauma population in the study.

[0301] As used herein, "about" means "within ±10%" with respect to an amount or value.

[0302] The terms "comprises," "comprising," "includes," "including," "having," and conjugations thereof mean "including but not limited to."

[0303] The term "consisting of" means "including and limited to."

[0304] The term "consisting essentially of" means that a composition, method, or structure may include additional components, steps, and / or moieties, provided that the additional components, steps, and / or moieties do not materially alter the basic and novel characteristics of the claimed composition, method, or structure.

[0305] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. For example, "a compound" or "at least one compound" includes a plurality of compounds, and can also include mixtures thereof.

[0306] Throughout this application, various embodiments of the invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and is not an inflexible limitation on the scope of the invention. Thus, the description of a range should be considered to specifically disclose all of the possible subranges and individual numerical values ​​within that range. For example, description of a range such as 1 to 6 specifically discloses subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numerical values ​​within that range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the magnitude of the range.

[0307] When a range of values ​​is provided herein (e.g., "10-15," "10 to 15," or any set of numbers connected by these other range designations), it is intended to include any number (fractional or integer) within the limits of the range provided, unless the context clearly dictates otherwise. The phrases "range between" a first designated number and a second designated number, and "range," "range to," "range to," or "range including" (or other similar range terminology) "from" a first designated number to a second designated number, are used interchangeably herein and are meant to include the first and second designated numbers and all fractional and integer numbers therebetween.

[0308] Unless otherwise indicated, numbers used herein, and any numerical ranges based thereon, are approximations within the accuracy of reasonable measurement and rounding errors, as will be understood by one of ordinary skill in the art.

[0309] As used herein, the term "method" means manner, means, techniques, and procedures for accomplishing a given task, including, but not limited to, those known to practitioners in the fields of chemistry, pharmacology, biology, biochemistry, and medicine, or those that can be readily developed by practitioners from known manners, means, techniques, and procedures.

[0310] As used herein, the term "treating" includes arresting, substantially inhibiting, slowing, or reversing the progression of a condition, substantially ameliorating the clinical or cosmetic symptoms of a condition, or substantially preventing the worsening of the clinical or cosmetic symptoms of a condition.

[0311] It will be understood that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in any combination of these features in a single embodiment. Conversely, multiple features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or with respect to other described embodiments as appropriate. A given feature described in the context of various embodiments should not be construed as essential to that embodiment, unless the particular embodiment is inoperable without that element.

[0312] While the present invention has been described in conjunction with specific embodiments thereof, many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and broad scope of the appended claims.

[0313] It is the intention of the applicants that all publications, patents, and patent applications mentioned in this specification be incorporated herein by reference in their entirety to the same extent as if each individual publication, patent, and patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application should not be construed as an admission that such reference is available as prior art to the present invention. Nor should it necessarily be construed as limiting, to the extent that section headings are used. In addition, the priority document of this application, if any, is incorporated herein by reference in its entirety.

Claims

1. 1. A method of treating a patient population for post-traumatic stress disorder (PTSD), comprising: Selecting a population of patients diagnosed with PTSD; administering NF treatment to said population; achieving an average reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of 8 to 12 weeks of said administration; A method comprising:

2. said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof. The method of claim 1.

3. training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the brain region or at least one biomarker thereof when exposed to at least one interface. The method of claim 2.

4. the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals. The method of claim 3.

5. A method of treating a patient population for post-traumatic stress disorder (PTSD), Selecting a population of patients diagnosed with PTSD; administering NF treatment to said population for a period of 8 to 12 weeks; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of no more than 3 months from said administration; A method comprising:

6. said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof. The method of claim 5.

7. training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the brain region or at least one biomarker thereof when exposed to at least one interface. The method of claim 6.

8. the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals. The method of claim 7.

9. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of female patients diagnosed with PTSD; administering NF treatment to said population; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of at least 8 weeks of said administration; A method comprising:

10. said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof.

10. The method of claim 9.

11. training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the at least one associated brain region or at least one biomarker thereof when exposed to at least one interface. The method of claim 10.

12. the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals. The method of claim 11.

13. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of male patients diagnosed with PTSD; administering NF treatment to said population; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of at least 8 weeks of said administration; A method comprising:

14. said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof. The method of claim 13.

15. training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the at least one associated brain region or at least one biomarker thereof when exposed to at least one interface.

15. The method of claim 14.

16. the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

16. The method of claim 15.

17. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of patients diagnosed with PTSD resulting from non-civil trauma; administering NF treatment to said selected population; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population after a period of at least 8 weeks of said administration; A method comprising:

18. said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof.

18. The method of claim 17.

19. training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the at least one associated brain region or at least one biomarker thereof when exposed to at least one interface.

20. The method of claim 18.

20. the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

20. The method of claim 19.

21. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of patients diagnosed with PTSD due to civil trauma; administering NF treatment to said selected population; achieving a mean reduction of at least 6 points on the CAPS-5 scale in said selected population at least 8 weeks after said administration; A method comprising:

22. said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof.

22. The method of claim 21.

23. training comprises training the selected population with the NF treatment to modulate the activation of the amygdala or the activation of the brain region or at least one biomarker thereof when exposed to at least one interface.

23. The method of claim 22.

24. the administered NF treatment comprises: recording EEG signals from the selected population during the exposure to the at least one interface; extracting from the recorded EEG signals one or more signals selectively indicative of an activity level of the amygdala or an activity level of the at least one associated brain region or the at least one biomarker thereof; and providing feedback to the population regarding the activity of the amygdala or regarding the activity of the at least one associated brain region or regarding the at least one biomarker thereof based on the one or more extracted signals.

24. The method of claim 23.

25. 1. A method for assessing the success of NF treatment in a PTSD patient, comprising: Selecting a patient diagnosed with PTSD; administering NF treatment to the selected patient; assessing the success of the NF treatment in the patient after a period of 8 to 12 weeks of the administration; A method comprising:

26. further comprising extending or suspending said enforcement based on the results of said evaluation.

26. The method of claim 25.

27. and further comprising extending said administration based on the results of said evaluation and providing additional treatment to said patient.

26. The method of claim 25.

28. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of female patients diagnosed with PTSD; administering NF treatment to said population; said administering includes training said selected female population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof when exposed to at least one interface. method.

29. and said administering said NF treatment comprises recording EEG signals from said selected population during said exposure to said at least one interface, extracting from said recorded EEG signals one or more signals selectively indicative of an activity level of said amygdala or an activity level of said at least one associated brain region or said at least one biomarker thereof, and providing feedback to said population regarding the activity of said amygdala or regarding the activity of said at least one associated brain region or regarding said at least one biomarker thereof based on said one or more extracted signals.

29. The method of claim 28.

30. and modifying the at least one interface based on the one or more extracted signals indicative of the activity level of the amygdala or the activity level of the at least one associated brain region or the at least one biomarker thereof.

30. The method of claim 29.

31. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of male patients diagnosed with PTSD; administering NF treatment to said population; and wherein said administering comprises training said selected male population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface. method.

32. and said administering said NF treatment comprises recording EEG signals from said selected population during said exposure to said at least one interface, extracting from said recorded EEG signals one or more signals selectively indicative of an activity level of said amygdala or an activity level of said at least one associated brain region or said at least one biomarker thereof, and providing feedback to said selected population regarding the activity of said amygdala or regarding the activity of said at least one associated brain region or regarding said at least one biomarker thereof based on said one or more extracted signals.

32. The method of claim 31 .

33. and modifying the at least one interface based on the one or more extracted signals indicative of the activity level of the amygdala or the activity level of the at least one associated brain region or the at least one biomarker thereof.

33. The method of claim 32.

34. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of patients diagnosed with PTSD resulting from non-civil trauma; administering NF treatment to said selected population; said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface. method.

35. and said administering said NF treatment comprises recording EEG signals from said selected population during said exposure to said at least one interface, extracting from said recorded EEG signals one or more signals selectively indicative of an activity level of said amygdala or an activity level of said at least one associated brain region or said at least one biomarker thereof, and providing feedback to said selected population regarding the activity of said amygdala or regarding the activity of said at least one associated brain region or regarding said at least one biomarker thereof based on said one or more extracted signals.

35. The method of claim 34.

36. 1. A method of treating a patient population for PTSD, comprising: Selecting a population of patients diagnosed with PTSD due to civil trauma; administering NF treatment to said selected population; said administering includes training said selected population with said NF treatment to modulate activation of the amygdala or activation of at least one associated brain region or at least one biomarker thereof upon exposure to at least one interface. method.

37. and said administering said NF treatment comprises recording EEG signals from said selected population during said exposure to said at least one interface, extracting from said recorded EEG signals one or more signals selectively indicative of an activity level of said amygdala or an activity level of said at least one associated brain region or said at least one biomarker thereof, and providing feedback to said selected population regarding the activity of said amygdala or regarding the activity of said at least one associated brain region or regarding said at least one biomarker thereof based on said one or more extracted signals.

37. The method of claim 36.

38. 1. A system for administering neurofeedback therapy for the treatment of PTSD, comprising: at least one user interface configured to provide at least one notification; a control unit having a memory and a control circuit; the memory stores at least one protocol of neurofeedback (NF) therapy or notification of such protocol; The control circuitry is configured to administer the NF treatment to the PTSD patient based on the at least one protocol stored in the memory or a notification of the protocol, and to signal the at least one user interface to generate a notification with information for evaluating the results of the NF treatment within a period of 8 to 12 weeks from the start of administration of the NF treatment. system.

39. the control circuitry is configured to receive an input signal including information regarding a result of the evaluation, and to signal the at least one user interface to generate a notification with information including a suggestion to modify the at least one NF treatment protocol or to discontinue administration of the NF treatment in response to the result of the evaluation.

39. The system of claim 38.

40. 1. A method for assessing the success of NF treatment in a PTSD patient, comprising: receiving results of at least one assessment of the PTSD patient conducted after initiation of the NF treatment in the PTSD patient; determining a relationship between the evaluation results and an expected evaluation result; generating a notification based on the determined relationship; and A method comprising:

41. determining includes determining that a result of the assessment is lower than the expected assessment result, and generating includes generating the notification with instructions to modify at least one parameter of the NF treatment and administer at least one additional NF treatment session of the NF treatment using the modified at least one NF treatment parameter.

41. The method of claim 40.

42. the at least one NF treatment parameter includes a duration of the NF treatment session, a number of additional NF treatment sessions, a type and / or content of a visual interface presented to the patient during the NF treatment session, and an analysis performed on EEG signals recorded from the subject's brain during the NF treatment session, the analysis being performed to detect modulation of activity of at least one of a limbic network, at least one limbic brain region, and an amygdala brain region based solely on the EEG signals; 42. The method of claim 41.

43. 1. A system for assessing the success of NF treatment, comprising: a memory for storing results of at least one assessment of the PTSD patient conducted after initiation of the NF treatment in the PTSD patient, and a predicted outcome of the assessment; control circuitry configured to determine a relationship between the stored result of the at least one evaluation and the stored expected outcome, and to generate a notification in response to the determined relationship; Including, the system.

44. the control circuitry is configured to determine that a result of the assessment is lower than the expected result and to generate the notification with instructions to modify at least one parameter of the NF treatment and to administer at least one additional NF treatment session of the NF treatment to the PTSD patient using the modified at least one NF treatment parameter.

44. The system of claim 43.

45. 1. A method for assessing the success of NF treatment in a group of PTSD patients, comprising: receiving results of at least one assessment in the group of PTSD patients conducted after initiation of the NF treatment in the PTSD patients; determining a relationship between the evaluation results and an expected evaluation result; generating a notification based on the determined relationship; and A method comprising:

46. processing the received results to generate individual assessment results for at least one subclass of the group of PTSD patients, and determining includes determining a relationship between the individual assessment results and the predicted assessment results for the at least one subclass of PTSD patients.

46. ​​The method of claim 45.

47. the at least one subclass of PTSD patients includes at least one of female PTSD patients, male PTSD patients, PTSD patients whose PTSD is caused by civil trauma, and PTSD patients whose PTSD is caused by non-civil trauma; 47. The method of claim 46.

48. 1. A system for assessing the success of NF treatment, comprising: a memory for storing results of at least one assessment performed on the group of PTSD patients after initiation of the NF treatment in the PTSD patients, and a predicted outcome of the assessment; control circuitry configured to determine a relationship between the stored result of the at least one assessment and the stored expected assessment outcome, and to generate a notification in response to the determined relationship; Including, the system.

49. the control circuitry is configured to process the received results to generate an individual assessment result for at least one subclass of the group of PTSD patients, and to determine a relationship between the individual assessment result for the at least one subclass of PTSD patients and the predicted assessment result.

49. The system of claim 48.

50. the at least one subclass of PTSD patients includes at least one of female PTSD patients, male PTSD patients, PTSD patients whose PTSD is caused by civil trauma, and PTSD patients whose PTSD is caused by non-civil trauma; 50. The system of claim 49.

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