Impact of Specialized Versus Non-Specialized Acute Hospital Care on Survival Among Patients With Acute Incomplete Traumatic Spinal Cord Injuries: A Population-Based Observational Study from British Columbia, Canada.

Given the complexity of care necessitated after an acute traumatic spinal cord injury (SCI), it seems intuitively beneficial for such care to be delivered at hospitals with specialized SCI expertise. Demonstrating these benefits is not straightforward, however. We sought to determine whether specialized acute hospital care influenced the most fundamental outcomes after SCI: mortality within the first year of injury. We compared survival among patients with incomplete tSCI admitted to a single quaternary-level trauma hospital with a specialized acute SCI program versus those admitted to trauma hospitals without specialized acute SCI care. We performed a population-based retrospective observational cohort study using administrative and clinical data linked from multiple sources in British Columbia (BC) from 2001 to 2017. Among a cohort of 1920 patients, there were 193 deaths within one year. We failed to identify a significant overall benefit for survival after adjusting for potential confounders, and the confidence intervals (CIs) were compatible with both benefit and harm (odds ratio [OR] 1.01, 95% CI 0.17 to 6.11, p = 0.99). Significant associations were observed with age greater than 65 (OR 4.92, 95% CI 1.66 to 14.57, p < 0.01), Charlson Comorbidity Index (OR 1.61, 95% CI 1.42 to 1.83, p < 0.01), Injury Severity Score (OR 1.08, 95% CI 1.06 to 1.11, p < 0.01), and traumatic brain injury (OR 2.12, 95% CI 1.32 to 3.41, p < 0.01). Among patients with acute tSCI, admission to a hospital with specialized acute SCI care was not associated with improved overall one-year survival. Subgroup analyses, however, suggested heterogeneity of effects, with little benefit for older patients with less polytrauma and substantial benefit for younger patients with greater polytrauma.

Advanced neuroimaging: A window into the neural correlates of fetal programming related to prenatal exposure to maternal depression and SSRIs.

Fetal programming is a conceptual framework whereby the in utero environment shapes the offspring's neurodevelopment. Maternal depression and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy are common prenatal exposures that affect critical early life developmental programming processes. Prenatal depression and SSRIs both have been reported to increase the risks for preterm birth, low birth weight, and are associated with behavioral disturbances across the early life span. However, not all exposures lead to adverse developmental outcomes and distinguishing how each exposure contributes to variations in development remains challenging. Advances in neuroimaging, using MR and EEG, offer novel insights into central processes that might reveal the neural correlates of fetal programming. This review focuses on emerging findings from neuroimaging studies reflecting early brain functional and structural development associated with prenatal exposure to maternal depression and SSRI antidepressants. Suggestions for future research directions that use neuroimaging as a tool to advancing our understanding of the early origins of developmental plasticity are offered.

Hub distribution of the brain functional networks of newborns prenatally exposed to maternal depression and SSRI antidepressants.

BACKGROUND: Prenatal maternal depression (PMD) and selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with increased developmental risk in infants. Reports suggest that PMD is associated with hyperconnectivity of the insula and the amygdala, while SSRI exposure is associated with hyperconnectivity of the auditory network in the infant brain. However, associations between functional brain organization and PMD and/or SSRI exposure are not well understood. METHODS: We examined the relation between PMD or SSRI exposure and neonatal brain functional organization. Infants of control (n = 17), depressed SSRI-treated (n = 20) and depressed-only (HAM-D ≥ 8) (n = 16) women, underwent resting-state functional magnetic resonance imaging at postnatal Day 6. At 6 months, temperament was assessed using Infant Behavioral Questionnaire (IBQ). We applied GTA and partial least square regression (PLSR) to the resting-state time series to assess group differences in modularity, and connector and provincial hubs. RESULTS: Modularity was similar across all groups. The depressed-only group showed higher connector hub values in the left anterior cingulate, insula, and caudate as well as higher provincial hub values in the amygdala compared to the control group. The SSRI group showed higher provincial hub values in Heschl's gyrus relative to the depressed-only group. PLSR showed that newborns' hub values predicted 10% of the variability in infant temperament at 6 months, suggesting different developmental patterns between groups. CONCLUSIONS: Prenatal exposures to maternal depression and SSRIs have differential impacts on neonatal functional brain organization. Hub values at 6 days predict variance in temperament between infant groups at 6 months of age.

Alterations in Resting-State Networks Following In Utero Selective Serotonin Reuptake Inhibitor Exposure in the Neonatal Brain.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression during pregnancy. SSRIs cross the placenta, inhibit serotonin reuptake, and thereby are thought to alter central fetal serotonin signaling. Both prenatal maternal mood disturbances and in utero SSRI exposure have been associated with altered fetal and infant behavior. Resting-state functional magnetic resonance imaging has identified resting-state networks (RSNs) in newborns, reflecting functional capacity of auditory and visual networks and providing opportunities to examine early experiences effects on neurodevelopment. We sought to examine the effect of in utero SSRI exposure on neonatal RSN functional organization. We hypothesized that prenatal SSRI exposure would be associated with alterations in neonatal RSNs compared with healthy control infants and infants exposed to mothers with depression. METHODS: Clinician-rated Hamilton Depression Rating Scale and self-reported Pregnancy Experiences Scale were completed during the third trimester. Control (n = 17), maternal depression-exposed (Hamilton Depression Rating Scale ≥8 without SSRI exposure, n = 16), and SSRI-exposed (n = 20) 6-day-old neonates underwent resting-state functional magnetic resonance imaging. Independent component analysis was used as a data-driven approach to extract 22 RSNs. RESULTS: SSRI-exposed neonates had higher connectivity in a putative auditory RSN compared with depressed-only (p = .01) and control (p = .02) infants (corrected for multiple comparisons), controlling for sex, age at the magnetic resonance imaging, and Pregnancy Experiences Scale score. CONCLUSIONS: Hyperconnectivity in auditory RSN in neonates with in utero SSRI exposure relative to neonates of depressed but not pharmacologically treated mothers and control infants may offer an insight into the functional organization origins of shifts in language perception and altered language development, previously reported in infants and children with prenatal SSRI exposure.

Variations in Neurodevelopmental Outcomes in Children with Prenatal SSRI Antidepressant Exposure.

Mood disorders and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy are common and both pose neurodevelopmental risks. This often makes the decision to treat prenatal depression with pharmacotherapy (i.e., antidepressants) challenging for clinicians and mothers. SSRIs block the reuptake of the neurotransmitter serotonin (5HT) and given its developmental role, it is not inconceivable that early changes in 5HT signaling could have an impact on early brain development. Identifying long-term neurodevelopmental effects of prenatal SSRI exposure is challenging in humans due to difficulties in distinguishing the effect of the drug from mother's mood during pregnancy and everyday environment in which the child lives, all of which contribute to shaping emotional, cognitive, and social development long after birth. In this review, we focus on the long-term neurobehavioral effects in childhood illustrating wide variations in outcomes revealing that some, but not all children appear to be affected by prenatal SSRI exposure. Emerging research reports findings that are beginning to distinguish the impact of genetic factors and the environment from prenatal medication exposure. Future research is needed to identify genetic, maternal, and environmental factors that put some children at developmental risk and others who may even benefit from maternal SSRI treatment. Birth Defects Research 109:909-923, 2017.© 2017 Wiley Periodicals, Inc.

Network analysis of perception-action coupling in infants.

The functional networks that support action observation are of great interest in understanding the development of social cognition and motor learning. How infants learn to represent and understand the world around them remains one of the most intriguing questions in developmental cognitive neuroscience. Recently, mathematical measures derived from graph theory have been used to study connectivity networks in the developing brain. Thus far, this type of analysis in infancy has only been applied to the resting state. In this study, we recorded electroencephalography (EEG) from infants (ages 4-11 months of age) and adults while they observed three types of actions: (a) reaching for an object; (b) walking; and (c) object motion. Graph theory based analysis was applied to these data to evaluate changes in brain networks. Global metrics that provide measures of the structural properties of the network (characteristic path, density, global efficiency, and modularity) were calculated for each group and for each condition. We found statistically significant differences in measures for the observation of walking condition only. Specifically, in comparison to adults, infants showed increased density and global efficiency in combination with decreased modularity during observation of an action that is not within their motor repertoire (i.e., independent walking), suggesting a less structured organization. There were no group differences in global metric measures for observation of object motion or for observation of actions that are within the repertoire of infants (i.e., reaching). These preliminary results suggest that infants and adults may share a basic functional network for action observation that is sculpted by experience. Motor experience may lead to a shift towards a more efficient functional network.

Post-hypoxic recovery of respiratory rhythm generation is gender dependent.

The preBötzinger complex (preBötC) is a critical neuronal network for the generation of breathing. Lesioning the preBötC abolishes respiration, while when isolated in vitro, the preBötC continues to generate respiratory rhythmic activity. Although several factors influence rhythmogenesis from this network, little is known about how gender may affect preBötC function. This study examines the influence of gender on respiratory activity and in vitro rhythmogenesis from the preBötC. Recordings of respiratory activity from neonatal mice (P10-13) show that sustained post-hypoxic depression occurs with greater frequency in males compared to females. Moreover, extracellular population recordings from the preBötC in neonatal brainstem slices (P10-13) reveal that the time to the first inspiratory burst following reoxygenation (TTFB) is significantly delayed in male rhythmogenesis when compared to the female rhythms. Altering activity of ATP sensitive potassium channels (KATP) with either the agonist, diazoxide, or the antagonist, tolbutamide, eliminates differences in TTFB. By contrast, glucose supplementation improves post-hypoxic recovery of female but not male rhythmogenesis. We conclude that post-hypoxic recovery of respiration is gender dependent, which is, in part, centrally manifested at the level of the preBötC. Moreover, these findings provide potential insight into the basis of increased male vulnerability in a variety of conditions such as Sudden Infant Death Syndrome (SIDS).