Heart Rate Variability and Pulse Rate Variability: Do Anatomical Location and Sampling Rate Matter?

Wearable technology and neuroimaging equipment using photoplethysmography (PPG) have become increasingly popularized in recent years. Several investigations deriving pulse rate variability (PRV) from PPG have demonstrated that a slight bias exists compared to concurrent heart rate variability (HRV) estimates. PPG devices commonly sample at ~20-100 Hz, where the minimum sampling frequency to derive valid PRV metrics is unknown. Further, due to different autonomic innervation, it is unknown if PRV metrics are harmonious between the cerebral and peripheral vasculature. Cardiac activity via electrocardiography (ECG) and PPG were obtained concurrently in 54 participants (29 females) in an upright orthostatic position. PPG data were collected at three anatomical locations: left third phalanx, middle cerebral artery, and posterior cerebral artery using a Finapres NOVA device and transcranial Doppler ultrasound. Data were sampled for five minutes at 1000 Hz and downsampled to frequencies ranging from 20 to 500 Hz. HRV (via ECG) and PRV (via PPG) were quantified and compared at 1000 Hz using Bland-Altman plots and coefficient of variation (CoV). A sampling frequency of ~100-200 Hz was required to produce PRV metrics with a bias of less than 2%, while a sampling rate of ~40-50 Hz elicited a bias smaller than 20%. At 1000 Hz, time- and frequency-domain PRV measures were slightly elevated compared to those derived from HRV (mean bias: ~1-8%). In conjunction with previous reports, PRV and HRV were not surrogate biomarkers due to the different nature of the collected waveforms. Nevertheless, PRV estimates displayed greater validity at a lower sampling rate compared to HRV estimates.

Temporal Pattern of Cortical Hypoxia in Multiple Sclerosis and Its Significance on Neuropsychological and Clinical Measures of Disability.

OBJECTIVE: Multiple sclerosis (MS) is a degenerative disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal damage. It has been hypothesized that hypoxia plays a role in the pathogenesis of MS. This study was undertaken to investigate the reproducibility of non-invasively measured cortical microvascular hemoglobin oxygenation (St O2 ) using frequency domain near-infrared spectroscopy (fdNIRS), investigate its temporal pattern of hypoxia in people with MS (pwMS), and its relationship with neurocognitive function and mood. METHODS: We investigated the reproducibility of fdNIRS measurements. We measured cortical hypoxia in pwMS, and the relationships between St O2 , neurocognitive function, fatigue, and measures of physical disability. Furthermore, we cataloged the temporal pattern of St O2 measured at 1-week intervals for 4 weeks, and at 8 weeks and ~1 year. RESULTS: We show that fdNIRS parameters were highly reproducible in 7 healthy control participants measured over 6 days (p > 0.05). There was low variability between and within subjects. In line with our previous findings, we show that 33% of pwMS (n = 88) have cortical microvascular hypoxia. Over 8 weeks and at ~1 year, St O2 values for normoxic and hypoxic groups did not change significantly. There was no significant association between cognitive function and St O2 . This conclusion should be revisited as only a small proportion of the relapsing-remitting MS group (21%) was cognitively impaired. INTERPRETATION: The fdNIRS parameters have high reproducibility and repeatability, and we have demonstrated that hypoxia in MS is a chronic condition, lasting at least a year. The results show a weak relationship between cognitive functioning and oxygenation, indicating future study is required. ANN NEUROL 2023;94:1067-1079.

Brain hypoxia, neurocognitive impairment, and quality of life in people post-COVID-19.

OBJECTIVE: Systemic hypoxia occurs in COVID-19 infection; however, it is unknown if cerebral hypoxia occurs in convalescent individuals. We have evidence from other conditions associated with central nervous system inflammation that hypoxia may occur in the brain. If so, hypoxia could reduce the quality of life and brain function. This study was undertaken to assess if brain hypoxia occurs in individuals after recovery from acute COVID-19 infection and if this hypoxia is associated with neurocognitive impairment and reduced quality of life. METHODS: Using frequency-domain near-infrared spectroscopy (fdNIRS), we measured cerebral tissue oxygen saturation (StO2) (a measure of hypoxia) in participants who had contracted COVID-19 at least 8 weeks prior to the study visit and healthy controls. We also conducted neuropsychological assessments and health-related quality of life assessments, fatigue, and depression. RESULTS: Fifty-six percent of the post-COVID-19 participants self-reported having persistent symptoms (from a list of 18), with the most reported symptom being fatigue and brain fog. There was a gradation in the decrease of oxyhemoglobin between controls, and normoxic and hypoxic post-COVID-19 groups (31.7 ± 8.3 µM, 27.8 ± 7.0 µM and 21.1 ± 7.2 µM, respectively, p = 0.028, p = 0.005, and p = 0.081). We detected that 24% of convalescent individuals' post-COVID-19 infection had reduced StO2 in the brain and that this relates to reduced neurological function and quality of life. INTERPRETATION: We believe that the hypoxia reported here will have health consequences for these individuals, and this is reflected in the correlation of hypoxia with greater symptomology. With the fdNIRS technology, combined with neuropsychological assessment, we may be able to identify individuals at risk of hypoxia-related symptomology and target individuals that are likely to respond to treatments aimed at improving cerebral oxygenation.

Objective Hemodynamic Cardiovascular Autonomic Abnormalities in Post-Acute Sequelae of COVID-19.

BACKGROUND: Many COVID-19 patients are left with symptoms several months after resolution of the acute illness; this syndrome is known as post-acute sequalae of COVID-19 (PASC). We aimed to determine the prevalence of objective hemodynamic cardiovascular autonomic abnormalities (CAA), explore sex differences, and assess the prevalence of CAA among hospitalized vs nonhospitalized patients with PASC. METHODS: Patients with PASC (n = 70; female [F] = 56; 42 years of age; 95% confidence interval [CI], 40-48) completed standard autonomic tests, including an active stand test 399 days (338, 455) after their COVID-19 infection. Clinical autonomic abnormalities were evaluated. RESULTS: Most patients with PASC met the criteria for at least 1 CAA (51; 73%; F = 43). The postural orthostatic tachycardia syndrome hemodynamic (POTSHR) criterion of a heart rate increase of > 30 beats per minute within 5 to 10 minutes of standing was seen in 21 patients (30%; F = 20; P = 0.037 [by sex]). The initial orthostatic hypotension hemodynamic (IOH40) criterion of a transient systolic blood pressure change of > 40 mm Hg in the first 15 seconds of standing was seen in 43 (61%) patients and equally among female and male patients (63% vs 57%; P = 0.7). Only 9 (13%) patients were hospitalized; hospitalized vs nonhospitalized patients had similar frequencies of abnormalities (67% vs 74%; P = 0.7). CONCLUSIONS: Patients with PASC have evidence of CAA, most commonly IOH40, which will be missed unless an active stand test is used. Female patients have increased frequency of POTSHR, but IOH40 is equally prevalent between sexes. Finally, even nonhospitalized "mild" infections can result in long-term CAAs.

NIRS Studies Show Reduced Interhemispheric Functional Connectivity in Individuals with Multiple Sclerosis That Exhibit Cortical Hypoxia.

Many with multiple sclerosis (MS) have low cortical microvascular oxygen levels (hypoxia), which have been previously proposed to exacerbate inflammation in MS. We do not know if hypoxia impacts or relates to brain function. We hypothesise that within the MS population, those who have hypoxia may show reduced brain functional connectivity (FC). We recruited 20 MS participants and grouped them into normoxic and hypoxic groups (n = 10 in each group) using frequency-domain near-infrared spectroscopy (fdNIRS). Functional coherence of the haemodynamic signal, quantified with functional near-infrared spectroscopy (fNIRS) was used as a marker of brain function and was carried out during resting-state, finger-tapping, and while completing two neurocognitive tasks. Reduced FC was detected in the hypoxic MS group. fNIRS measures of haemodynamic coherence in MS could be a biomarker of functional impairment and/or disease progression.

Insufficient sampling frequencies skew heart rate variability estimates: Implications for extracting heart rate metrics from neuroimaging and physiological data.

BACKGROUND: While cardiac pulsations are widely present within physiological and neuroimaging data, it is unknown the extent this information can provide valid and reliable heart rate and heart rate variability (HRV) estimates. The objective of this study was to demonstrate how a slight temporal shift due to an insufficient sampling frequency can impact the validity/accuracy of deriving cardiac metrics. METHODS: Twenty-two participants were instrumented with valid/reliable industry-standard or open-source electrocardiograms. Five-minute lead II recordings were collected at 1000 Hz in an upright orthostatic position. Following artifact removal, the 1000 Hz recording for each participant was downsampled to frequencies ranging 2-500 Hz. The validity of each participant's downsampled recording was compared against their 1000 Hz recording ("reference-standard") using Bland-Altman plots with 95 % limits of agreement (LOA), coefficient of variation (CoV), intraclass correlation coefficients, and adjusted r-squared values. RESULTS: Downsampled frequencies of ≥ 50 and ≥ 90 Hz produced highly robust measures with narrow log-transformed 95 % LOA (<±0.01) and low CoV values (≤3.5 %) for heart rate and HRV metrics, respectively. Below these thresholds, the log-transformed 95 % LOA became wider (LOA range: ±0.1-1.9) and more variable (CoV range: 1.5-111.6 %). CONCLUSION: These results provide an important consideration for obtaining cardiac information from physiological data. Compared to the "reference-standard" ECG, a seemingly negligible temporal shift of the systolic contraction (R wave) greater than 11-milliseconds (90 Hz) away from its true value, lessened the validity of the HRV. Further research is warranted to determine the minimum sampling frequency required to obtain valid heart rate/HRV metrics from pulsatile waveforms.

Internal Consistency of Sway Measures via Embedded Head-Mounted Accelerometers: Implications for Neuromotor Investigations.

Accelerometers are being increasingly incorporated into neuroimaging devices to enable real-time filtering of movement artifacts. In this study, we evaluate the reliability of sway metrics derived from these accelerometers in a standard eyes-open balance assessment to determine their utility in multimodal study designs. Ten participants equipped with a head-mounted accelerometer performed an eyes-open standing condition on 7 consecutive days. Sway performance was quantified with 4 standard metrics: root-mean-square (RMS) acceleration, peak-to-peak (P2P) acceleration, jerk, and ellipse area. Intraclass correlation coefficients (ICC) quantified reliability. P2P in both the mediolateral (ICC = 0.65) and anteroposterior (ICC = 0.67) planes yielded the poorest reliability. Both ellipse area and RMS exhibited good reliability, ranging from 0.76 to 0.84 depending on the plane. Finally, jerk displayed the highest reliability with an ICC value of 0.95. Moderate to excellent reliability was observed in all sway metrics. These findings demonstrate that head-mounted accelerometers, commonly found in neuroimaging devices, can be used to reliably assess sway. These data validate the use of head-mounted accelerometers in the assessment of motor control alongside other measures of brain activity such as electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS).

The validity and reliability of an open source biosensing board to quantify heart rate variability.

BACKGROUND: Heart rate variability (HRV) is a popular tool to quantify autonomic function. However, this typically requires an expensive 3-12 lead electrocardiogram (ECG) and BioAmp system. This investigation sought to determine the validity and reliability of an OpenBCI cyton biosensing board (open source) for accurately quantifying HRV. NEW METHOD: A cyton board with a 3-lead ECG was employed to acquire heart rate waveform data, which was processed to obtain HRV within both time- and frequency-domains. The concurrent validity was compared to a simultaneous recording from an industry-standard 3-lead ECG (ADInstruments) (n = 15). The reliability of the cyton board was compared between three days within a 7-day timespan (n = 10). Upright quiet-stance short-term HRV metrics were quantified in time- and frequency-domains. RESULTS: The two devices displayed excellent limits of agreements (all log mean differences ±0.4) and very high between-device variable associations (all r 2 > 0.98). Between the three time points in the same subjects, no differences were noted within time- (all p > 0.71) or frequency-domains (all p > 0.88) across testing points. Finally, all HRV metrics exhibited excellent levels of reliability through high Cronbach's Alpha (all ≥0.916) and intraclass correlation coefficients (all ≥0.930); and small standard error of the measurement (all ≤0.7) and typical error of the measurement (all ≤0.1) metrics. COMPARISON WITH EXISTING METHODS: The cyton board with 3-lead ECG was compared with an industry-standard ADInstruments ECG during HRV assessments. There were no significant differences between devices with respect to time- and frequency-domains. The cyton board displayed high-levels of between-day reliability and provided values harmonious to previous ECG literature highlighting the applicability for longitudinal studies. CONCLUSION: With proper background knowledge regarding ECG principles and a small degree of set-up complexity, an open source cyton board can be created and employed to perform multimodal HRV assessments at a fraction of the cost (~4%) of an industry-standard ECG setup.