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Martin G Frasch

Publications and source records attributed to Martin G Frasch.

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Future of Brain Health: From Developmental Insights to Clinical Translation

This review highlights brain health as a dynamic process shaped by both genetic and environmental influences throughout development. Critical periods provide unique windows of heightened neural plasticity, during which genetic-environmental interactions and parental influences profoundly impact brain maturation. Frameworks such as DOHaD, ACEs, and neurosocial plasticity elucidate how early-life experiences modulate long-term cognitive and emotional outcomes. Brain health science is emerging as a field integrating neuroscience, public health, and social context. Resilience-oriented approaches and predictive processing, offer renewed perspectives on adaptive brain function. Clinically, understanding critical periods and plasticity spanning from fetal life to old age, has implications for early detection, targeted interventions, and resilience-oriented strategies, emphasizing the potential for lifelong optimization of mental health.

q-bio.NC

Inter-Electrode Pulse Wave Velocity: A Direct Method for Maternal Arterial Stiffness Assessment During Pregnancy Using Multi-Channel ECG

Objective: To validate a novel inter-electrode pulse wave velocity (PWV) method that measures pulse propagation between ECG electrodes without left ventricular ejection time (LVET) estimation. Methods: We analyzed 43 three-channel ECG recordings (1000 Hz) from the FELICITy 2 cohort (approximately 19 and 35 weeks gestation). R-peaks were independently detected per channel using an ensemble approach. Time lags (Delta t) between matched R-peaks across electrode pairs were used to compute PWV as PWV = L / Delta t, where L is effective inter-electrode distance. Three channel pairs yielded independent PWV estimates. Temporal stability was assessed using sliding windows (1-15 minutes). To test whether Delta t reflects morphology or vascular propagation, we evaluated three QRS fiducials (R-peak, QRS onset, maximum dV/dt) and two bandpass filters (0.5-40 and 0.5-100 Hz). Longitudinal changes were compared between control (n=24) and yoga (n=20) groups. Results: PWV values were physiologically plausible and consistent with aortic PWV (5-10 m/s): control 7.40 +/- 1.51 vs 6.98 +/- 1.63 m/s; yoga 7.10 +/- 2.15 vs 8.16 +/- 0.91 m/s (early vs late pregnancy). PWV stabilized at 5 minutes (coefficient of variation 12.3 percent), with 2.6- to 5.2-fold lower variability than heart rate and heart rate variability. Inter-electrode delays (15-27 ms) persisted across fiducials and were minimally affected by filter settings (change -8.5 percent, not significant), arguing against purely morphological distortion; PWV remained within 6.8-9.1 m/s. Preliminary group trends differed (control -5.7 percent, yoga +14.9 percent; interaction p=0.07). Conclusions: Inter-electrode PWV enables direct spatial assessment of pulse propagation with physiologically valid values, is robust to fiducial and filtering choices, and shows promise for pregnancy-related arterial stiffness assessment with standard multi-channel ECG.

physics.med-ph

Dose-Dependent Cardiac Complexity Changes in Children Following Prenatal Glucocorticoid Exposure: Complementary Evidence from Multiscale Entropy Analysis and ECG Foundation Models

\noindent\textbf{Background} Prenatal glucocorticoid exposure alters cardiac development, but whether persistent cardiac effects in childhood follow a dose-response relationship remains unknown. We recently showed that ECG foundation models detect robust cardiac differences between steroid-exposed and control children, while traditional heart rate variability metrics lose significance after covariate adjustment. Here, we investigate the dose-response dimension using complementary analytical approaches. \noindent\textbf{Methods} We studied 49 children (ages 8--15) whose mothers received betamethasone during pregnancy for multiple sclerosis: 12 low-dose ({$<$}5\,g cumulative), 13 high-dose ({$\geq$}5\,g), and 24 controls. Five-minute ECG recordings during the Trier Social Stress Test yielded 251 observations. We computed 12 multiscale complexity features and tested 11 ECG foundation model (FM) dimensions using linear mixed models, Kruskal--Wallis tests with Dunn's post-hoc comparisons, Spearman correlations, and Jonckheere--Terpstra trend tests. \noindent\textbf{Findings} The binary exposed-versus-controls comparison showed no significant complexity effects ($p>0.39$). However, dose-based analysis revealed that high-dose children exhibited significantly faster entropy rate ($h$) decay rates than low-dose children ($p=0.031$); neither sample entropy nor approximate entropy decay rates reached significance ($p=0.18$ and $p=0.12$, respectively). Effects localized to the mental arithmetic stress segment (Kruskal--Wallis $p=0.005$; Dunn's $p=0.004$). A cross-condition robustness analysis confirmed that $h$ decay rate is invariant to input signal choice and normalization ($r>0.98$), while sample and approximate entropy are not. In contrast, the 11 FM dimensions showed weak dose-response evidence: only 1 of 22 covariate-adjusted contrasts survived FDR correction, with paradoxically stronger low-dose effects. \noindent\textbf{Interpretation} The entropy rate decay rate -- uniquely robust across input conditions -- reveals a dose-dependent effect on cardiac autonomic dynamics under cognitive stress, while FM dimensions detect a dose-independent morphological ``exposure fingerprint.'' These exploratory findings suggest a two-component model of prenatal glucocorticoid cardiac programming -- ~morphological (dose-independent) and dynamical (dose-dependent)~ -- providing more complete characterization than either approach alone. Given the small sample size, these results should be considered hypothesis-generating and require replication in larger cohorts.

q-bio.QM

Heart Rate Variability Patterns Reflect Yoga Intervention in Chronically Stressed Pregnant Women: A Quasi-Randomized Controlled Trial

Prenatal maternal stress (PS) is a risk factor for adverse offspring neurodevelopment. Heart rate variability (HRV) complexity provides a non-invasive marker of maternal autonomic regulation and may be influenced by mind--body interventions such as Yoga. In this quasi-randomized controlled trial, 28 chronically stressed pregnant women were followed from the second trimester until birth: 14 participated in weekly Hatha Yoga with electrocardiogram (ECG) recordings, and 14 received standard obstetric care with monthly ECGs. Group allocation was based on availability, with participants unaware of their assignment at enrollment. HRV complexity was assessed first with Sample Entropy and Entropy Rate and then expanded to 94 HRV metrics spanning temporal, frequency, nonlinear, and information-theoretical domains. All metrics were covariate-adjusted (maternal age, BMI, gestational age), standardized, and analyzed using timepoint-specific principal component analysis (PCA). From this, a unified HRV index was derived. Analyses revealed that HRV metric relationships changed dynamically across pregnancy, with PCA loadings shifting from frequency toward complexity measures in late gestation. The mixed effects model identified a significant time x group interaction effect (p = 0.041). These findings suggest a restructuring of HRV signal-analytical domains with advancing pregnancy attributable to Yoga and highlight the utility of advanced HRV analysis frameworks for future, larger trials.

q-bio.QM

Can a composite heart rate variability biomarker shed new insights about autism spectrum disorder in school-aged children?

High-frequency heart rate variability (HRV) has identified parasympathetic nervous system alterations in autism spectrum disorder (ASD). In a cohort of school-aged children with and without ASD, we test a set of alternative linear and nonlinear HRV measures, including phase rectified signal averaging, applied to a segment of resting ECG, for associations with ASD vs. other psychiatric conditions. Using machine learning, we identify HRV measures derived from time, frequency, and geometric signal-analytical domains that (1) identify children with ASD relative to peers with receiver operating curve area of .89, and (2) differentiate such children from those with conduct problems or depression. Despite the small cohort and lack of prospective external validation, these preliminary results warrant larger prospective validation studies.

q-bio.QM