Disturbances of neural oscillation patterns have been reported with many disease states. We introduce methodology for HIRREM™ (high-resolution, relational, resonance-based electroencephalic mirroring), also known as Brainwave Optimization™, a noninvasive technology to facilitate relaxation and auto-calibration of neural oscillations. HIRREM is a precision-guided technology for allostatic therapeutics, intended to help the brain calibrate its own functional set points to optimize fitness. HIRREM technology collects electroencephalic data through two-channel recordings and delivers a series of audible musical tones in near real time. Choices of tone pitch and timing are made by mathematical algorithms, principally informed by the dominant frequency in successive instants of time, to permit resonance between neural oscillatory frequencies and the musical tones. Relaxation of neural oscillations through HIRREM appears to permit auto-calibration toward greater hemispheric symmetry and more optimized proportionation of regional spectral power. To illustrate an application of HIRREM, we present data from a randomized clinical trial of HIRREM as an intervention for insomnia (n = 19). On average, there was reduction of right-dominant temporal lobe high-frequency (23–36 Hz) EEG asymmetry over the course of eight successive HIRREM sessions. There was a trend for correlation between reduction of right temporal lobe dominance and magnitude of insomnia symptom reduction. Disturbances of neural oscillation have implications for both neuropsychiatric health and downstream peripheral (somatic) physiology. The possibility of noninvasive optimization for neural oscillatory set points through HIRREM suggests potentially multitudinous roles for this technology. Research is currently ongoing to further explore its potential applications and mechanisms of action.

A bihemispheric autonomic model (BHAM) may support advanced understanding of traumatic stress effects on physiology and behavior. The model builds on established data showing hemispheric lateralization in management of the autonomic nervous system, and proposes that traumatic stress can produce dominant asymmetry in activity of bilateral homologous brain regions responsible for autonomic management. Rightward and leftward dominant asymmetries are associated with sympathetic high arousal or parasympathetic freeze tendencies, respectively, and return to relative symmetry is associated with improved autonomic regulation. Autonomic auto-calibration for recovery (inverse of Jacksonian dissolution proposed by polyvagal theory) has implications for risk behaviors associated with traumatic life stress. Trauma-induced high arousal may be associated with risk for maladaptive behaviors to attenuate arousal (including abuse of alcohol or sedative-hypnotics). Trauma-induced freeze mode (including callous-unemotional trait) may be associated with low resting heart rate and risk for conduct disorders. The model may explain higher prevalence of leftward hemispheric abnormalities reported in studies of violence. Implications of the BHAM are illustrated through case examples of a military special operations officer with history of traumatic brain injury and post-traumatic stress disorder, and a university student with persisting post-concussion symptoms. Both undertook use of a noninvasive closed-loop neurotechnology – high-resolution, relational, resonance-based, electroencephalic mirroring – with ensuing decrease in hemispheric asymmetry, improvement in heart rate variability, and symptom reduction. Finally, the BHAM aligns with calls for researchers to use brain-behavioral constructs (research domain criteria or RDoC, proposed by the National Institutes of Mental Health) as building blocks for assessment and intervention in mental health science.

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.

Effective noninvasive interventions for insomnia are needed. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM™) is a noninvasive, electroencephalography (EEG)-based method to facilitate greater client-unique, autocalibrated improvements of balance and harmony in cortical neural oscillations. This study explores using HIRREM for insomnia. Twenty subjects, with an Insomnia Severity Index (ISI) score of ≥15 (14 women, mean age 45.4, mean ISI 18.6), were enrolled in this randomized, unblinded, wait-list control, crossover, superiority study. Subjects were randomized to receive 8–12 HIRREM sessions over 3 weeks, plus usual care (HUC), or usual care alone (UC). Pre- and post-HIRREM data collection included ISI (primary outcome), and many secondary, exploratory measures (CES-D, SF-36, HR, BP, neurocognitive testing, and VAS scales). The UC group later crossed over to receive HIRREM. ISI was also repeated 4–6 weeks post-HIRREM. All subjects completed the primary intervention period. Analysis for differential change of ISI in the initial intervention period for HUC versus UC showed a drop of 10.3 points (95% CI: −13.7 to −6.9, P < 0.0001, standardized effect size of 2.68). Key secondary outcomes included statistically identical differential change for the crossed-over UC group, and persistence of the effect on the ISI up to > 4 weeks post-HIRREM. Differential change in the HUC group was also statistically significant for CES-D (−8.8, 95% CI: −17.5 to −0.1, P = 0.047), but other exploratory outcomes were not statistically significant. For all receiving HIRREM (n = 19), decreased high-frequency total power was seen in the bilateral temporal lobes. No adverse events were seen. This pilot clinical trial, the first using HIRREM as an intervention, suggests that HIRREM is feasible and effective for individuals having moderate-to-severe insomnia, with clinically relevant, statistically significant benefits based on differential change in the ISI. Effects persisted for 4 weeks after completion of HIRREM. Larger controlled clinical trials are warranted.

BackgroundThe objective of this pilot study was to explore the use of a closed-loop, allostatic, acoustic stimulation neurotechnology for individuals with self-reported symptoms of post-traumatic stress, as a potential means to impact symptomatology, temporal lobe high frequency asymmetry, heart rate variability (HRV), and baroreflex sensitivity (BRS).MethodsFrom a cohort of individuals participating in a naturalistic study to evaluate use of allostatic neurotechnology for diverse clinical conditions, a subset was identified who reported high scores on the Posttraumatic Stress Disorder Checklist (PCL). The intervention entailed a series of sessions wherein brain electrical activity was monitored noninvasively at high spectral resolutions, with software algorithms translating selected brain frequencies into acoustic stimuli (audible tones) that were delivered back to the user in real time, to support auto-calibration of neural oscillations. Participants completed symptom inventories before and after the intervention, and a subset underwent short-term blood pressure recordings for HRV and BRS. Changes in temporal lobe high frequency asymmetry were analyzed from baseline assessment through the first four sessions, and for the last four sessions.ResultsNineteen individuals (mean age 47, 11 women) were enrolled, and the majority also reported symptom scores that exceeded inventory thresholds for depression. They undertook a median of 16 sessions over 16.5 days, and 18 completed the number of sessions recommended. After the intervention, 89% of the completers reported clinically significant decreases in post-traumatic stress symptoms, indicated by a change of at least 10 points on the PCL. At a group level, individuals with either rightward (n = 7) or leftward (n = 7) dominant baseline asymmetry in temporal lobe high frequency (23–36 Hz) activity demonstrated statistically significant reductions in their asymmetry scores over the course of their first four sessions. For 12 individuals who underwent short-term blood pressure recordings, there were statistically significant increases in HRV in the time domain and BRS (Sequence Up). There were no adverse events.ConclusionClosed-loop, allostatic neurotechnology for auto-calibration of neural oscillations appears promising as an innovative therapeutic strategy for individuals with symptoms of post-traumatic stress.Trials registrationClinicalTrials.gov #NCT02709369, retrospectively registered on March 4, 2016.