Evaluation of neurovascular coupling during neuroprotective therapies: A single site HEAL ancillary study.

Background: There is a critical need for development of physiological biomarkers in infants with birth asphyxia to identify the physiologic response to therapies in real time. This is an ancillary single site study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (Wu et al., 2022 [1]) to measure neurovascular coupling (NVC) non-invasively during an ongoing blinded randomized trial.

Feasibility of EEG Phase-Amplitude Coupling to Stratify Encephalopathy Severity in Neonatal HIE Using Short Time Window.

Goal: It is challenging to clinically discern the severity of neonatal hypoxic ischemic encephalopathy (HIE) within hours after birth in time for therapeutic decision-making for hypothermia. The goal of this study was to determine the shortest duration of the EEG based PAC index to provide real-time guidance for clinical decision-making for neonates with HIE. Methods: Neonates were recruited from a single-center Level III NICU between 2017 and 2019.

EEG phase-amplitude coupling to stratify encephalopathy severity in the developing brain.

Background: Neonatal hypoxic ischemic encephalopathy (HIE) is difficult to classify within the narrow therapeutic window of hypothermia. Neurophysiological biomarkers are needed for timely differentiation of encephalopathy severity within the short therapeutic window for initiation of hypothermia therapy.

Methods: A novel analysis of mean Phase Amplitude Coupling index, PAC, of amplitudes high frequencies (12-30 Hz) coupled with phases of low (1,2 Hz) frequencies was calculated from the 6 h EEG recorded during the first day of life.

Wavelet-based neurovascular coupling can predict brain abnormalities in neonatal encephalopathy.

Background: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in neonates, but quantitative methods to predict outcomes early in their course of illness remain elusive. Real-time physiologic biomarkers of neurologic injury are needed in order to predict which neonates will benefit from therapies. Neurovascular coupling (NVC) describes the correlation of neural activity with cerebral blood flow, and the degree of impairment could predict those at risk for poor outcomes.

EEG Spectral Power: A Proposed Physiological Biomarker to Classify the Hypoxic-Ischemic Encephalopathy Severity in Real Time.

Background: Mild hypoxic-ischemic encephalopathy (HIE) constitutes a large unstudied population with considerable debate on how to define and treat due to the dynamic evolution of the clinical signs of encephalopathy. We propose to address this gap with quantitative physiological biomarkers to aid in stratification of the disease severity. The objectives of this prospective cohort study were to measure the electroencephalographic (EEG) power as an objective biomarker of the evolution of the clinical encephalopathy in newborns with mild to severe HIE.

Neurovascular coupling (NVC) in newborns using processed EEG versus amplitude-EEG.

There is a critical need for development of real time physiological biomarkers for birth asphyxia that constitutes a major global public health burden. Our recent study (Scientific Reports, V10:9183, 2020) established a novel non-invasive neurovascular coupling (NVC) assessment in newborns using dynamic wavelet transform coherence (WTC) analysis irrespective of different aEEG algorithms. As an extended study, the current paper examines whether the variability in processed EEG and amplitude-EEG (aEEG) outputs would impact the determination of NVC in newborns with encephalopathy.

Cerebral cortical autonomic connectivity in low-risk term newborns.

Purpose: The mature central autonomic network includes connectivity between autonomic nervous system brainstem centers and the cerebral cortex. The study objective was to evaluate the regional connectivity between the cerebral cortex and brainstem autonomic centers in term newborns by measuring coherence between high-density electroencephalography and heart rate variability as measured by electrocardiography.

Methods: Low-risk term newborns with birth gestational age of 39-40 weeks were prospectively enrolled and studied using time-synced electroencephalography and electrocardiography for up to 60 min before discharge from the birth hospital.

Hippocampal Theta Oscillations Support Successful Associative Memory Formation.

Models of memory formation posit that episodic memory formation depends critically on the hippocampus, which binds features of an event to its context. For this reason, the contrast between study items that are later recollected with their associative pair versus those for which no association is made fails should reveal electrophysiological patterns in the hippocampus selectively involved in associative memory encoding. Extensive data from studies in rodents support a model in which theta oscillations fulfill this role, but results in humans have not been as clear.

Rigor of Neurovascular Coupling (NVC) Assessment in Newborns Using Different Amplitude EEG Algorithms.

Birth asphyxia constitutes a major global public health burden for millions of infants with a critical need for real time physiological biomarkers. This proof of concept study targets the translational rigor of such biomarkers and aims to examine whether the variability in the amplitude-integrated EEG (aEEG) outputs impact the determination of neurovascular coupling (NVC) in newborns with encephalopathy. A convenience sample with neonatal asphyxia were monitored for twenty hours in the first day of life with EEG and near infrared spectroscopy (NIRS)-based cerebral tissue oxygen saturation (SctO2).

Regional heterogeneity of cerebral hemodynamics in mild neonatal encephalopathy measured with multichannel near-infrared spectroscopy.

Background: Neuromonitoring at the bedside is the key to understand the pathophysiological mechanisms of brain injury associated with neonatal encephalopathy. The current practice is to monitor the forehead using a noninvasive cerebral oximetry-it remains unknown to what extent cerebral hemodynamics in other brain regions is different to the frontal region.

Method: A multichannel near-infrared spectroscopy (NIRS) system was used to monitor neonates (n = 14) with fetal acidosis and mild neonatal encephalopathy at four brain regions (the frontal, posterior, left temporal, and right temporal lobes).

Prognostic Value of Continuous Electroencephalogram Delta Power in Neonates With Hypoxic-Ischemic Encephalopathy.

The objective was to examine the discriminatory ability of electroencephalogram (EEG) delta power in neonates with hypoxic-ischemic encephalopathy (HIE) with well-defined outcomes. Prolonged continuous EEG recordings from term neonates with HIE during therapeutic hypothermia enrolled in a prospective observational study were examined. Adverse outcome was defined as death or severe brain injury by magnetic resonance imaging (MRI); favorable outcome was defined as normal or mild injury by MRI.

Effect of EKG Sampling Rate on Heart Rate Variability Analysis.

We studied the effect of EKG sampling rate on heart rate variability (HRV) analysis. We acquired EKG from four term hypoxic-ischemic encephalopathic infants undergoing therapeutic hypothermia. The EKG signal was acquired continuously for 4 days from the cardiorespiratory monitor through the analog port.

The effect of labor and delivery mode on electrocortical and brainstem autonomic function during neonatal transition.

Delivery of the newborn occurs either vaginally or via caesarean section. It is not known whether the mode of delivery and exposure to labor affects early autonomic nervous system (ANS) function, as measured by heart rate variability (HRV), or cortical electroencephalogram (EEG) activity. The objective of the study was to determine if autonomic function in newborns differs by mode of delivery.

Construction of a species-specific vector for improved plastid transformation efficiency in L.

In the present study, we focused on designing a species-specific chloroplast vector for L. and finding out its transformation efficiency compared to a heterologous vector. The plastid transformation vector (CaIA) was designed to target homologous regions and of IR region.

The effect of unilateral stroke on autonomic function in the term newborn.

Background: The mature cerebral cortex has a topographically organized influence on reflex autonomic centers of the brainstem and diencephalon and sympathetic activation coming primarily from the right hemisphere and parasympathetic activation from the left. In the term newborn, the maturational status of this central autonomic system remains poorly understood.

Methods: Sixteen term newborns admitted to Children's National with unilateral middle cerebral artery (MCA) strokes (n = 8 left, n = 8 right) had archived continuous electrocardiograph (EKG) signals available.

Autonomic nervous system depression at term in neurologically normal premature infants.

Background: Premature infants are vulnerable to destructive brain injury and disturbed neurological development. Prematurity may alter maturation of the central autonomic nervous system (ANS).

Aims: To compare ANS function (using heart rate variability; HRV) between preterm infants with normal neuroimaging at term equivalent age and low-risk term controls.

Autonomic Dysfunction in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia Impairs Physiological Responses to Routine Care Events.

Objective: To evaluate whether infants with hypoxic-ischemic encephalopathy and evidence of autonomic dysfunction have aberrant physiological responses to care events that could contribute to evolving brain injury.

Study Design: Continuous tracings of heart rate (HR), blood pressure (BP), cerebral near infrared spectroscopy, and video electroencephalogram data were recorded from newborn infants with hypoxic-ischemic encephalopathy who were treated with hypothermia. Videos between 16 and 24 hours of age identified 99 distinct care events, including stimulating events (diaper changes, painful procedures), and vagal stimuli (endotracheal tube manipulations, pupil examinations).

Construction of chloroplast transformation vector and its functional evaluation in L.

Chloroplast transformation vectors require an expression cassette flanked by homologous plastid sequences to drive plastome recombination. The 16-23 plastome region was selected and using this region, a new species-specific plastid transformation vector CuIA was developed with pKSII as a backbone by inserting the 16- and -23 sequences from L. An independent expression cassette with gene encoding aminoglycoside 3'-adenylyltransferase with controlling elements is added into the - intergenic region that confers resistance to spectinomycin.

Efficient genetic transformation of L. by microprojectile bombardment.

Here, we report the optimized conditions for biolistic particle delivery-mediated genetic transformation of bitter melon using petiole segments. In this study, DNA-coated gold particles of 0.6 µm were used for optimizing the parameters of transformation and eventually regeneration of bitter melon putative transgenics.

A frequency based spatial filter to mitigate volume conduction in electroencephalogram signals.

Volume conduction is a major problem in spatial-temporal electroencephalogram (EEG) signals. We propose a frequency dependent subtraction approach to address the volume conduction problem in EEG signals. We validate the proposed approach using simulated data and discuss the application of the approach to the EEG data recorded from three sick infants.

Stable plastid transformation in L.

In the present investigation we report stable plastid transformation in L., a versatile medicinal herb via particle gun method. The vector KNTc, harbouring as a selectable marker and as a reporter gene which were under the control of synthetic promoter pNG1014a, targets inverted repeats, / of the plastid genome.