Papers by Angela Fenoglio

Developmental Psychobiology, 2022
Infants born preterm are more likely than ever to survive, but relatively little is known about t... more Infants born preterm are more likely than ever to survive, but relatively little is known about the factors that influence their subsequent sociocognitive development. Responding to joint attention (RJA) is a pivotal skill that is likely supported by biological preparedness at birth and ex-utero social experience. The goals of this study are to evaluate the relative roles of chronological age, gestation duration, and birthweight for early RJA and examine birthweight as a potential moderator of the associations between chronological age and RJA. This study leveraged a mixed longitudinal design of infants (N = 256, obs = 421) from 8 to 16 months of chronological age. Results show that chronological age and gestation duration both explain unique variation in RJA. Further, birthweight exhibits quadratic relations with RJA. Birthweight moderates the association between chronological age and RJA; infants born heavier demonstrate faster RJA growth compared to those born smaller. Findings suggest that birth weight, an index of nutrient sufficiency in utero and biological preparedness, may constrain or afford early RJA development, consistent with the Developmental Origins of Health and Disease (DoHAD) hypothesis. Findings inform our understanding of the roles of biological preparedness and experience in shaping RJA and help disaggregate potential mechanisms of prematurity-related challenges to social cognitive development.

Understanding the evolution of regional and hemispheric asymmetries in the early stages of life i... more Understanding the evolution of regional and hemispheric asymmetries in the early stages of life is essential to the advancement of developmental neuroscience. By using 2 noninvasive optical methods, frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy, we measured cerebral hemoglobin oxygenation (SO2), blood volume (CBV), an index of cerebral blood flow (CBFi), and the metabolic rate of oxygen (CMRO2i) in the frontal, temporal, and parietal regions of 70 premature and term newborns. In concordance with results obtained using more invasive imaging modalities, we verified both hemodynamic (CBV, CBFi, and SO2) and metabolic (CMRO2i) parameters were greater in the temporal and parietal regions than in the frontal region and that these differences increased with age. In addition, we found that most parameters were significantly greater in the right hemisphere than in the left. Finally, in comparing age-matched males and females, we found that males had higher ...

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there i... more Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.

When considering the use of emerging technologies, counseling becomes complex when it is unclear ... more When considering the use of emerging technologies, counseling becomes complex when it is unclear whether the level of evidence is sufficient to transform the proposed therapy into accepted practice. This paper addresses the ethical issues underlying medical decision-making and counseling in the setting of emerging treatments, when long-term outcomes are still in the process of being fully validated. We argue that the ethical transition of emerging technologies, ideally from ethically impermissible to ethically permissible to ethically obligatory, depends primarily on two factors: outcome data (or prognosis) and treatment feasibility. To illustrate these points, we will use intestinal transplant for short bowel syndrome (SBS) as a specific example. After reviewing the data, this paper will identify the ethical justifications for both comfort care only (CCO) and intestinal transplant in patients with ultra SBS, and argue that both are ethically permissible, but neither is obligatory. ...
University of Minnesota Ph.D. dissertation. August 2019. Major: Psychology. Advisor: Jed Elison. ... more University of Minnesota Ph.D. dissertation. August 2019. Major: Psychology. Advisor: Jed Elison. 1 computer file (PDF); iv, 91 pages.

The Journal of Pediatrics, 2018
Objective-To characterize restricted and repetitive behaviors (RRBs) and reciprocal social behavi... more Objective-To characterize restricted and repetitive behaviors (RRBs) and reciprocal social behaviors (RSBs) in a large sample of toddlers who represent a range of birth weights and gestation durations. Study design-A battery of questionnaires characterizing demographic information and measuring RRBs and RSBs were completed by parents of toddlers between the ages of 17-26 months (n = 1589 total; n = 98 preterm). The association between birth weight and/or gestation duration and the primary outcome measures (RRBs and RSBs as ascertained through the Repetitive Behavior Scale for Early Childhood and the Video-Referenced Rating of Reciprocal Social Behavior) were tested by using hierarchical multivariate multiple regression. Results-Toddlers born preterm and full term did not differ on RRBs or RSBs. However, there were significant associations between birth weight percentile for gestation duration (BPGD) and RRBs (β = −2.1, P = .03), above and beyond the effects of age, sex, and vocabulary production. Similarly, there was a significant association between BPGD and RSBs (β = −1.8, P = .02), above and beyond the effects of age, sex, and vocabulary production. Conclusions-These findings demonstrate that BPGD better predicted putative antecedents of adverse psychological outcomes-specifically, RRBs and RSBs-than gestation duration alone. These findings provide insight to the link between preterm birth and suboptimal behavioral/ psychological outcomes and suggest that high birth weight, which may reflect a more optimal intrauterine environment, may serve as a protective factor irrespective of gestation duration. Children born preterm are more likely to exhibit symptoms consistent with autism spectrum disorder (ASD), 1,2 and children born very preterm (<30 weeks of gestation) are at 3 times greater risk for developing psychiatric diagnoses, including anxiety disorders, attentiondeficit/hyperactivity disorder, and ASD. 3 Moderate-to-late preterm birth (32-36 weeks of

Journal of Neurodevelopmental Disorders, 2017
Preterm birth is associated with an increased risk of adverse neurologic, psychiatric, and cognit... more Preterm birth is associated with an increased risk of adverse neurologic, psychiatric, and cognitive outcomes. The brain circuits involved in processing social information are critical to all of these domains, but little work has been done to examine whether and how these circuits may be especially sensitive to prematurity. This paper contains a brief summary of some of the cognitive, psychiatric, and social outcomes associated with prematurity, followed by a description of findings from the modest body of research into social-cognitive development in infants and children born preterm. Next, findings from studies of structural and functional brain development in infants born preterm are reviewed, with an eye toward the distinctive role of the brain circuits implicated in social functioning. The goal of this review is to investigate the extent to which the putative "social brain" may have particular developmental susceptibilities to the insults associated with preterm birth, and the role of early social-cognitive development in later neurodevelopmental outcomes. Much work has been done to characterize neurobehavioral outcomes in the preterm population, but future research must incorporate both brain and behavioral measures to identify early biomarkers linked to later emerging social-cognitive clinical impairment in order to guide effective, targeted intervention.

Scientific reports, May 16, 2016
Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in... more Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant's bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower ...

Critical Care Medicine
As a first step to sudy the plant community socio-ecologically, it is necessary to determine the ... more As a first step to sudy the plant community socio-ecologically, it is necessary to determine the production of matter, therefore analytically the standing crop and the productive structure of the community (Boysen-Jensen 1932, Monsi 1954). From this point of view some works have recently been done by Monsi and Saeki (1953), and Hogetsu, Ichimura et al, (1954) on the land plant community. On the phytoplankton community, also Hogetsu and Ichimura (1954), Ichimura (1954) have worked in similar direction. Although in addition to these works we have many descriptive works on the ecology of water plant, yet there remain many problems on the water plant community that should be fundamentally investigated and solved. In the present paper, the author deals mainly with the results of the survey in some lakes of central Japan, and he discusses the dry matter production and the productive structure of phytoplankton community.
Biomedical Optics 2014, 2014
ABSTRACT By using noninvasive optical techniques, we detected lower cerebral blood flow and metab... more ABSTRACT By using noninvasive optical techniques, we detected lower cerebral blood flow and metabolism in extremely premature neonates with low-grade intraventricular hemorrhage at the age of 4 to 8 weeks.

Journal of Visualized Experiments, 2013
Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there i... more Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO 2 ). Thus, measures of CMRO 2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO 2 an ideal target for bedside measurement of brain health. Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases. Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO 2 ) as a surrogate for cerebral oxygen consumption. However, SO 2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO 2 are not sensitive enough to detect brain injury hours after the insult 1,2 , because oxygen consumption and delivery reach equilibrium after acute transients 3 . We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO 2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBF i ) to yield an index of CMRO 2 (CMRO 2i ) 4,5 . With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

NeuroImage, 2014
The hemodynamic functional response is used as a reliable marker of neuronal activity in countles... more The hemodynamic functional response is used as a reliable marker of neuronal activity in countless studies of brain function and cognition. In newborns and infants, however, conflicting results have appeared in the literature concerning the typical response, and there is little information on brain metabolism and functional activation. Measurement of all hemodynamic components and oxygen metabolism is critical for understanding neurovascular coupling in the developing brain. To this end, we combined multiple near infrared spectroscopy techniques to measure oxy-and deoxy-hemoglobin concentrations, cerebral blood volume (CBV), and relative cerebral blood flow (CBF) in the somatosensory cortex of 6 preterm neonates during passive tactile stimulation of the hand. By combining these measures we estimated relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO 2 ). CBF starts increasing immediately after stimulus onset, and returns to baseline before blood volume. This is consistent with the model of pre-capillary arteriole active dilation driving the CBF response, with a subsequent CBV increase influenced by capillaries and veins dilating passively to accommodate the extra blood. rCMRO 2 estimated using the steady-state formulation shows a biphasic pattern: an increase immediately after stimulus onset, followed by a post-stimulus undershoot due to blood flow returning faster to baseline than oxygenation. However, assuming a longer mean transit time from the arterial to the venous compartment, due to the immature vascular system of premature infants, reduces the post-stimulus undershoot and increases the flow/ consumption ratio to values closer to adult values reported in the literature.

Journal of Cerebral Blood Flow & Metabolism, 2011
Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen c... more Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen consumption in the premature newborn brain. We combined quantitative frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation (SO2) and CBV with diffusion correlation spectroscopy measures of cerebral blood flow index (BFix) to determine the relationship between these measures, gestational age at birth (GA), and chronological age. We followed 56 neonates of various GA once a week during their hospital stay. We provide absolute values of SO2 and CBV, relative values of BFix, and relative cerebral metabolic rate of oxygen (rCMRO2) as a function of postmenstrual age (PMA) and chronological age for four GA groups. SO2 correlates with chronological age ( r=−0.54, P value 0.001) but not with PMA ( r=−0.07), whereas BFix and rCMRO2 correlate better with PMA ( r=0.37 and 0.43, respectively, P value 0.001). Relative CMRO2 during the first month of life is lower whe...

Cerebral Cortex, 2012
Understanding the evolution of regional and hemispheric asymmetries in the early stages of life i... more Understanding the evolution of regional and hemispheric asymmetries in the early stages of life is essential to the advancement of developmental neuroscience. By using 2 noninvasive optical methods, frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy, we measured cerebral hemoglobin oxygenation (SO 2), blood volume (CBV), an index of cerebral blood flow (CBF i), and the metabolic rate of oxygen (CMRO 2i) in the frontal, temporal, and parietal regions of 70 premature and term newborns. In concordance with results obtained using more invasive imaging modalities, we verified both hemodynamic (CBV, CBF i , and SO 2) and metabolic (CMRO 2i) parameters were greater in the temporal and parietal regions than in the frontal region and that these differences increased with age. In addition, we found that most parameters were significantly greater in the right hemisphere than in the left. Finally, in comparing age-matched males and females, we found that males had higher CBF i in most cortical regions, higher CMRO 2i in the frontal region, and more prominent right-left CBF i asymmetry. These results reveal, for the first time, that we can detect regional and hemispheric asymmetries in newborns using noninvasive optical techniques. Such a bedside screening tool may facilitate early detection of abnormalities and delays in maturation of specific cortical areas.

Brain Imaging and Behavior, 2013
Children with autism spectrum disorder (ASD) are highly variable in their language abilities, but... more Children with autism spectrum disorder (ASD) are highly variable in their language abilities, but the neural bases of these individual differences are poorly understood. Structural magnetic resonance imaging (MRI) and magnetic resonance diffusion tensor imaging (DTI) tractography were used to examine asymmetries in language-related gray-and white-matter and their relationships to language ability in a sample of 20 children with ASD, aged 4-7 years, and a reference sample of 20 typically developing (TD) children, aged 6-11 years. Children with ASD did not differ significantly from TD children in gray matter asymmetries, but were significantly less left-lateralized than TD children in the volume and radial diffusivity (RD) of the arcuate fasciculus (AF). They did not differ in the fractional anisotropy (FA) or the mean or axial diffusivity of the AF. Within the ASD group, exploratory analyses revealed that decreased leftward/increased rightward asymmetry of pars opercularis was associated with higher language ability and bilaterally increased FA and decreased RD of the AF. In conclusion, children with ASD exhibited atypical asymmetry in languagerelated white-matter structure as well as an atypical pattern of brain-language relationships that suggest that they may meet language milestones and acquire normal language via a different neurodevelopmental trajectory from TD children.
Methods: Seventy-two newborns (24-42 weeks PMA with no suspicion of brain injury were recruited t... more Methods: Seventy-two newborns (24-42 weeks PMA with no suspicion of brain injury were recruited to investigate regional and hemispheric cortical differences. We used a customized FDNIRS system (ISS Inc., Champaign, IL, USA) to measure SO2 and cerebral blood ...

Journal of Cerebral Blood Flow & Metabolism, 2013
Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associ... more Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow ( CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism ( CMRO2i) and CBF indices ( CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume ( CBV) and hemoglobin oxygen saturation ( SO2) were significantly higher in neonates with HIE during TH compared wit...
Biomedical Optics 2014, 2014
ABSTRACT In order to better understand the injured neonatal brain, we quantify cerebral oxygenati... more ABSTRACT In order to better understand the injured neonatal brain, we quantify cerebral oxygenation, blood flow, and oxygen metabolism in healthy neonates during the first days of life using non-invasive optical spectroscopies.
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Papers by Angela Fenoglio