Change in Center for Epidemiologic Studies Depression Scale (CES-D) Score From Baseline to 12 Days
The CES-D is a 20-item survey assessing affective depressive symptomatology to screen for risk of depression. Scores range from 0-60, with a score of 16 commonly used as a clinically relevant cut-off. Higher scores suggest more depressive symptomatology. Secondary outcome with the CES-D will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.
Change in Insomnia Severity Index (ISI) Score From Baseline to 12 Days
The severity of insomnia symptoms is measured using the ISI with each data collection visit. The ISI is a 7 question measure, with responses from 0-4 for each question, yielding scores ranging from 0-28. Higher scores indicate the strength of the insomnia severity. Secondary outcome with the ISI will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.
Change in Generalized Anxiety Disorder-7 (GAD-7) Score From Baseline to 12 Days
The Generalized Anxiety Disorder-7 (GAD-7) is a seven item screening tool for anxiety that is widely used in primary care. Each item is rated from 0 (not at all) to 3 (nearly every day). Scores range from 0 to 21 with higher scores suggesting more anxiety. Secondary outcome with the GAD-7 will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.
Change in Rivermead Post-Concussion Symptoms Questionnaire (RPQ) Score From Baseline to 12 Days
The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is a 16-item survey that assesses the severity of the most common post-concussion symptoms on a scale of 0 to 4, with a total score range from 0 to 64 (least to greatest symptom severity). Items are compared to levels before the head injury and are reported as a 24 hour recall. Secondary outcome with the RPQ will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.
Change in EQ-5D Score From Baseline to 12 Days
The EQ-5D is a brief, standardized measure of health status developed by the EuroQol Group, and is a paper and pencil survey providing a single index value for health status. Secondary outcome with the EQ-5D will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Global health rating question is reported (0-100, with 100 being in the best health possible).
Change in Heart Rate Variability Measure of SDNN From Baseline to 12 Days
Secondary autonomic outcome with heart rate variability will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Heart rate variability is measured in the time domain as standard deviation beat-to-beat interval (SDNN, milliseconds). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed. Higher SDNN values suggest better autonomic regulation.
Change in Baroreflex Sensitivity HF Alpha From Baseline to 12 Days
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard Baroreflex Sensitivity (BRS) software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the frequency domain as high frequency (HF) alpha index (ms2). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in HF alpha suggest better autonomic regulation.
Change in Baroreflex Sensitivity Sequence Up From Baseline to 12 Days
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard Baroreflex Sensitivity (BRS) software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence Up (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence Up suggest better autonomic regulation.
Change in Baroreflex Sensitivity Sequence Down From Baseline to 12 Days
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard Baroreflex Sensitivity (BRS) software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence Down (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence Down suggest better autonomic regulation.
Change in Baroreflex Sensitivity Sequence All From Baseline to 12 Days
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard Baroreflex Sensitivity (BRS) software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence All (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence All suggest better autonomic regulation.
Change in Drop Stick Reaction Time From Baseline to 12 Days
Reaction testing is measured by a drop-stick apparatus that has been validated as a way to quantify the impact of athletic concussion on psychomotor performance. Following two practice trials, participants perform eight trials, and a mean distance value is calculated. Secondary functional outcome with drop-stick reaction time will be analyzed for changes in distance from baseline to the in person data collection immediately after completion of the intervention. A lower average indicates a faster reaction time.
Change in Grip Strength From Baseline to 12 Days
Grip strength will evaluated using a hydraulic hand dynamometer (Baseline Hydraulic Hand Dynamometer, ranges from 0 to 300 lbs). Both right and left hand will be evaluated, and the greatest force generated during three trials will be used for analysis. A higher score indicates stronger grip strength.
Change in Functional MRI From Baseline to 12 Days
Anatomical and physiological brain imaging will be performed during a 1-hour imaging session at baseline and immediately following completion of the intervention. This will include imaging sequences such as high resolution structural scans. Brain network data will be collected using blood oxygenation level dependent (BOLD) scans. These scans will be collected under various states such as at rest. All images will be acquired using a 3 Tesla Siemens MRI scanner. Whole-brain network connectivity will be assessed using blood oxygenation level dependent (BOLD) imaging. Unit of measure is percentage of BOLD signal change. Community structure will be determined for each participant pre- and post-intervention. This project will focus on the community including the Default Mode Network (DMN). Participant strength of the community structure will be determined of the DMN. Permutation analysis will be used to evaluate significant pattern change in specific networks.
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days
Blood for a panel of biomarkers for stress will be collected at enrollment, and after completion of the intervention. The panel includes Ang II, Ang 1-7, Epinephrine, Norepinephrine, C-reactive protein, Vasopressin, IL-1, IL-6, and IL-10.
Salivary Biomarker Cortisol for Stress From Baseline to 12 Days
Saliva for salivary biomarker Cortisol, for stress, will be collected at enrollment, and after completion of the intervention.
Change in Epigenetic Markers From Baseline to 12 Days
DNA will be isolated from whole blood, collected in yellow-top Vacutainer tubes (ACD as the preservative), using the AutoPure LS system in the Genomics Center Core lab. DNA will be bisulfite-converted using the EZ DNA Methylation Gold kit (Zymo, Irvine, CA). To quantify DNA methylation at each site, investigators will use the HumanMethylationEPIC450 BeadChip (Illumina, Inc.). The methylation proportion for each site (beta value) is based on the ratio of the fluorescence intensity of the methylated versus the combined methylated & unmethylated probes, & will be determined with GenomeStudio (Illumina, Inc.). Ratio of 0 equals no methylation & ratio of 1 equals total (100%) methylation." Effects of DNA methylation for a specific site are dependent on function of the regulated gene(s). For some genes, increased level methylation from the intervention may be beneficial, while for others an increased level may be detrimental. There is no universal way to interpret change in DNA methylation.
Change in Sleep Latency Score From Baseline to 42 Days
An online daily sleep diary to calculate sleep latency will be maintained from baseline, through the one month post-intervention remote data collection (roughly 42 days). Sleep latency is reported in minutes and a smaller score suggests falling asleep faster.
Change in C-reactive Protein for Stress and Inflammation Score From Baseline to 12 Days
Blood for biomarker C-reactive protein for stress will be collected at enrollment, and after completion of the intervention.
Salivary Biomarker for Stress From Baseline to 12 Days
Saliva for salivary biomarker Alpha-Amylase, for stress, will be collected at enrollment, and after completion of the intervention.