Successful use of closed-loop allostatic neurotechnology for post-traumatic stress symptoms in military personnel: self-reported and autonomic improvements

Abstract

BackgroundMilitary-related post-traumatic stress (PTS) is associated with numerous symptom clusters and diminished autonomic cardiovascular regulation. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®) 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 auto-calibration of neural oscillations. We report clinical, autonomic, and functional effects after the use of HIRREM® for symptoms of military-related PTS.MethodsEighteen 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.ResultsClinically 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.ConclusionsService 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.

Functional Brain Network Changes Following Use of an Allostatic, Closed‐Loop, Acoustic Stimulation Neurotechnology for Military‐Related Traumatic Stress

“…The current study provides the first data showing changes in brain connectivity on resting‐state MRI among individuals with symptoms of military‐related PTS or PTSD, who undertook usage of an allostatic neurotechnology (HIRREM) for autocalibration of neural oscillations. There were postinterventional changes in connectivity in the DMN, sensorimotor, and visual circuits which may explain clinical benefits reported elsewhere . In contrast, the present study did not demonstrate significant changes in connectivity at the whole brain level or in the SN or CEN as a whole.…”

“…Because this study did not include a control group, it is not possible to quantify what portion of the network connectivity changes may have been due to usage of the neurotechnology intervention as such, rather than nonspecific treatment factors including subjective expectation and overall participation in a study intervention over 12 days. Nonetheless, the durability of the clinical improvements (to 6 months) as well as the autonomic cardiovascular changes reported elsewhere is not consistent with regression to the mean, the natural history of PTS(D) symptomatology, or typical characteristics of the placebo response. The statistical significance for the changes in the DMN (including anterior portion) as well as the SMN, corresponding to data that associate these regions to PTSD symptomatology and sleep respectively, suggests that those changes were due to intervention effects rather than natural variability in network connectivity.…”

“…The objective of this manuscript is to report brain network connectivity changes in military service members and recent Veterans with symptoms of military‐related traumatic stress who undertook usage of an allostatic, closed‐loop, acoustic stimulation neurotechnology. Reductions in self‐reported symptoms of post‐traumatic stress, insomnia, depression, and anxiety, as well as improvements in functional outcomes and autonomic cardiovascular regulation (heart rate variability and baroreflex sensitivity), in this same cohort, were recently reported . Symptom reduction was durable through the final online data collection 6 months after completion of the intervention.…”

“…The objective of this study is to evaluate clinical, physiological, physical functional, and brain connectivity changes associated with the use of HIRREM by military service members with traumatic stress symptoms. Funding allowed evaluation of the effect of HIRREM on functional brain networks for the first 18 participants enrolled, before and after the use of HIRREM over a 12‐day period …”

“…Additionally, they were asked to abstain from recreational drug and alcohol use until 1 month after the active portion of the study. More details regarding the cohort may be found in the recent report on clinical outcomes …”