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

ABSTRACT: BACKGROUND AND PURPOSE:Post-traumatic stress disorder is associated with connectivity changes in the default mode, central executive, and salience networks, and other brain regions. This study evaluated changes in network connectivity associated with usage of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM® ; Brain State Technologies, Scottsdale, AZ), a closed-loop, allostatic, acoustic stimulation neurotechnology, for military-related traumatic stress. METHODS:Eighteen participants (17 males, mean age 41 years [SD = 7], 15 active duty) enrolled in an IRB approved pilot trial for symptoms of military-related traumatic stress. Participants received 19.5 (1.1) HIRREM sessions over 12 days. Symptoms, physiological and functional measures, and whole brain resting MRI were collected before and after HIRREM. Six whole brain functional networks were evaluated using summary variables and community structure of predefined networks. Pre to postintervention change was analyzed using paired-sample statistical tests. RESULTS:Postintervention, there was an overall increase in connectivity of the default mode network (P = .0094). There were decreases of community structure in both the anterior portion of the default mode (medial prefrontal cortex, P = .0097) and in the sensorimotor (P = .005) network. There were no statistically significant changes at the whole brain level, or in the central executive, salience, or other networks analyzed. Participants demonstrated significant improvements in clinical symptoms, as well as autonomic cardiovascular regulation, which have been reported previously. CONCLUSIONS:Use of closed-loop, allostatic, acoustic stimulation neurotechnology (HIRREM) was associated with connectivity changes in the default mode and sensorimotor networks, in directions that may have explained the subjects' clinical improvements.

SUBMITTER: Lee SW

PROVIDER: S-EPMC6586033 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Lee Sung W SW Laurienti Paul J PJ Burdette Jonathan H JH Tegeler Catherine L CL Morgan Ashley R AR Simpson Sean L SL Gerdes Lee L Tegeler Charles H CH

Journal of neuroimaging : official journal of the American Society of Neuroimaging 20181010 1

<h4>Background and purpose</h4>Post-traumatic stress disorder is associated with connectivity changes in the default mode, central executive, and salience networks, and other brain regions. This study evaluated changes in network connectivity associated with usage of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM<sup>®</sup> ; Brain State Technologies, Scottsdale, AZ), a closed-loop, allostatic, acoustic stimulation neurotechnology, for military-related traumati ...[more]

PMID: 30302866

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Project description: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®) 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. 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. CONCLUSIONS: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.

Project description:BACKGROUND:Effective interventions are needed for individuals with persisting post-concussion symptoms. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®) is an allostatic, closed-loop, acoustic stimulation neurotechnology, designed to facilitate relaxation and self-optimization of neural oscillations. METHODS:Fifteen athletes (seven females, mean age 18.1 years, SD 2.6) with persisting post-concussion symptoms received 18.7 (SD 6.0) HIRREM sessions over a mean of 29.6 (SD 23.2) days, including 11.3 (SD 4.6) in office days. Pre- and post-HIRREM measures included the Rivermead Post-Concussion Symptoms Questionnaire (RPQ, n?=?12), the Insomnia Severity Index (ISI, n?=?15), the Center for Epidemiologic Studies Depression Scale (CES-D, n?=?10), short-term blood pressure and heart rate recordings for measures of autonomic cardiovascular regulation (n?=?15), and reaction time by the drop-stick method (n?=?7). All participants were asked about their physical activity level and sports participation status at their post-HIRREM data collection visit and 1 to 3 months afterward. RESULTS:At the post-HIRREM visit, subjects reported improvements in all three inventories (RPQ mean change 19.7, SD 11.4, Wilcoxon p?=?0.001; ISI mean change -4.1, SD 4.1, Wilcoxon p?=?0.003; CES-D mean change -12.0, SD 10.0, Wilcoxon p?=?0.004), including statistically significant reductions in 14 of the 16 individual items of the RPQ. There were also statistically significant improvements in baroreflex sensitivity, heart rate variability in the time domain (SDNN), and drop-stick reaction testing (baseline mean distance of 23.8 cm, SD 5.6, decreased to 19.8 cm, SD 4.6, Wilcoxon p?=?0.016). Within 3 months of the post-HIRREM data collection, all 15 had returned to full exercise and workouts, and ten had returned to full participation in their athletic activity. CONCLUSIONS:The use of HIRREM by a series of athletes with persisting post-concussion symptoms was associated with a range of improvements including, for the majority, return to full participation in their sport. The findings do not appear to be consistent with constituents of the placebo effect. A larger controlled trial is warranted.

Project description: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.

Project description:Background:Heart rate variability (HRV) is an indicator of dynamic adaptability of the autonomic nervous system. Few interventions target upstream, cerebral cortex components of the heart-brain system for autonomic management. We report changes in HRV and baroreflex sensitivity (BRS), associated with use of a noninvasive, closed-loop, allostatic, computer-guided, acoustic stimulation neurotechnology. Methods:Over 5?years, 220 subjects with heterogeneous neurological, cardiovascular, and psychophysiological conditions consecutively enrolled in a naturalistic, single-arm study exploring clinical effects associated with use of the neurotechnology. Of those, 202 completed the study protocol and 160 had recordings adequate to analyze HRV and BRS. Mean age was 44.0 (SD 19.4), with 130 women. Participants received a mean of 16.1 (5.2) sessions, over 24.2?days (23.3), with 9.5 (3.8) actual intervention days. Sessions included real-time analysis of brain electrical activity and software algorithm-guided translation of selected frequencies into patterns of acoustic stimulation (audible tones of variable pitch and timing), to facilitate auto-calibration of neural oscillations. Outcomes including 10-min supine, at-rest recordings of blood pressure and heart rate, and inventories for insomnia (ISI) and depression (CES-D or BDI-II), were obtained at baseline and 15.3 (16.7) days after the last session. Results:Compared to baseline, significant increases (all p?<?0.001) were observed for measures of HRV across all participants including the mean percentage change for SDNN 24.2% (SE 0.04), and RMSSD, 42.2% (0.08), and BRS [Sequence Up, 55.5% (0.09), Sequence Down, 77.6% (0.23), and Sequence All, 53.7% (0.07)]. Significant improvements were noted in SAP, MAP, and DAP, as well as natural log of HF, and total power. Self-reported ISI was reduced (ISI, -6.4 points, SD 5.6, p?<?0.001). The proportion reporting clinically significant depressive symptoms reduced from 48.2% at baseline to 22.1% at follow-up. Linear regression showed that rightward asymmetry predicted lower SDNN (p?=?0.02). Exploratory analysis showed a trend for improved balance of temporal lobe high-frequency amplitudes over the course of initial sessions. Conclusion:These findings indicate that use of a noninvasive, allostatic, closed-loop neurotechnology appears to have robust potential for public health efforts to support greater flexibility in autonomic cardiovascular regulation, through self-optimization of electrical activity at the level of the brain.

Dataset Information

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

Publications

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

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