摘要Background:Military-related post-traumatic stress (PTS) is associated with numerous symptom clusters and diminished autonomic cardiovascular regulation.High-resolution,relational,resonance-based,electroencephalic mirroring (HIRREM(R)) is a noninvasive,closed-loop,allostatic,acoustic stimulation neurotechnology that produces real-time translation of dominant brain frequencies into audible tones of variable pitch and timing to support the autocalibration of neural oscillations.We report clinical,autonomic,and functional effects after the use of HIRREM(R) for symptoms of military-related PTS.Methods:Eighteen service members or recent veterans (15 active-duty,3 veterans,most from special operations,1 female),with a mean age of 40.9(SD=6.9) years and symptoms of PTS lasting from 1 to 25 years,undertook 19.5(SD=1.1) sessions over 12 days.Inventories for symptoms of PTS (Posttraumatic Stress Disorder Checklist-Military version,PCL-M),insomnia (Insomnia Severity Index,ISI),depression (Center for Epidemiologic Studies Depression Scale,CES-D),and anxiety (Generalized Anxiety Disorder 7-item scale,GAD-7) were collected before (Visit 1,V1),immediately after (Visit 2,V2),and at 1 month (Visit 3,V3),3 (Visit 4,V4),and 6 (Visit 5,V5) months after intervention completion.Other measures only taken at V1 and V2 included blood pressure and heart rate recordings to analyze heart rate variability (HRV) and baroreflex sensitivity (BRS),functional performance (reaction and grip strength) testing,blood and saliva for biomarkers of stress and inflammation,and blood for epigenetic testing.Paired t-tests,Wilcoxon signed-rank tests,and a repeated-measures ANOVA were performed.Results:Clinically relevant,significant reductions in all symptom scores were observed at V2,with durability through V5.There were significant improvements in multiple measures of HRV and BRS [Standard deviation of the normal beat to normal beat interval (SDNN),root mean square of the successive differences (rMSSD),high frequency (HF),low frequency (LF),and total power,HF alpha,sequence all,and systolic,diastolic and mean arterial pressure] as well as reaction testing.Trends were seen for improved grip strength and a reduction in C-Reactive Protein (CRP),Angiotensin Ⅱ to Angiotensin 1-7 ratio and Interleukin-10,with no change in DNA n-methylation.There were no dropouts or adverse events reported.Conclusion:Service members or veterans showed reductions in symptomatology of PTS,insomnia,depressive mood,and anxiety that were durable through 6 months after the use of a closed-loop allostatic neurotechnology for the auto-calibration of neural oscillations.This study is the first to report increased HRV or BRS after the use of an intervention for service members or veterans with PTS.Ongoing investigations are strongly warranted.Trial registration:NCT03230890,retrospectively registered July 25,2017.