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2 Choline as a neurodevelopmental intervention for children with fetal alcohol spectrum disorder: Long-term associations with white matter microstructure and executive function
- Blake A. Gimbel, Mary E. Anthony, Abigail M. Ernst, Donovan J. Roediger, Erik de Water, Judith K. Eckerle, Christopher J. Boys, Joshua P. Radke, Bryon A. Mueller, Anita J. Fuglestad, Steven H. Zeisel, Michael K. Georgieff, Jeffrey R. Wozniak
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 613-614
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Objective:
Fetal alcohol spectrum disorder (FASD) is a life-long condition, and few interventions have been developed to improve the neurodevelopmental course in this population. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. In this study, we examine treatment group differences in executive function (EF) outcomes and diffusion MRI of the corpus callosum using the Neurite Orientation Dispersion and Density Index (NODDI) biophysical model.
Participants and Methods:The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5- to 5-year-olds with FASD. Participants in this long-term follow-up study included 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up evaluation included measures of executive functioning (WISC-V Picture Span and Digit Span; DKEFS subtests) and diffusion MRI (NODDI).
Results:Children who received choline early in development outperformed those in the placebo group across a majority of EF tasks at long-term follow-up (effect sizes ranged from -0.09 to 1.27). Children in the choline group demonstrated significantly better performance on several tasks of lower-order executive function skills (i.e., DKEFS Color Naming [Cohen's d = 1.27], DKEFS Word Reading [Cohen's d = 1.13]) and showed potentially better white matter microstructure organization (as indicated by lower orientation dispersion; Cohen's d = -1.26) in the splenium of the corpus callosum compared to the placebo group. In addition, when collapsing across treatment groups, higher white matter microstructural organization was associated with better performance on several EF tasks (WISC-V Digit Span; DKEFS Number Sequencing and DKEFS Word Reading).
Conclusions:These findings highlight long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that changes in white matter organization may represent an important target of choline in this population. Unique to this study is the use of contemporary biophysical modeling of diffusion MRI data in youth with FASD. Findings suggest this neuroimaging approach may be particularly useful for identifying subtle white matter differences in FASD as well as neurobiological responses to early intervention associated with important cognitive functions.
1 Sluggish Cognitive Tempo in Children and Adolescents with Fetal Alcohol Spectrum Disorders: Associations with Executive Function and Subcortical Volumes
- Abigail M Ernst, Blake A Gimbel, Mary E Anthony, Donovan J Roediger, Erik de Water, Bryon A Mueller, Sarah N Mattson, Kelvin O Lim, Jeffrey R Wozniak
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 612-613
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Objective:
Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental condition associated with deficits in cognitive functioning (executive functioning [EF], attention, working memory, etc.), behavioral impairments, and abnormalities in brain structure including cortical and subcortical volumes. Rates of comorbid attention-deficit/hyperactivity disorder (ADHD) are high in children with FASD and contribute to significant functional impairments. Sluggish cognitive tempo (SCT) includes a cluster of symptoms (e.g. underactive/slow-moving, confusion, fogginess, daydreaming) found to be related to but distinct from ADHD, and previous research suggests that it may be common in FASD. We explored SCT by examining the relationship between SCT and both brain volumes (corpus callosum, caudate, and hippocampus) and objective EF measures in children with FASD vs. typically developing controls.
Participants and Methods:This is a secondary analysis of a larger longitudinal CIFASD study that consisted of 35 children with prenatal alcohol exposure (PAE) and 30 controls between the ages of 9 to 18 at follow-up. Children completed a set of cognitive assessments (WISC-IV, DKEFS, & NIH Toolbox) and an MRI scan, while parents completed the Child Behavior Checklist (CBCL), which includes a SCT scale. We examined group differences between PAE and controls in relation to SCT symptoms, EF scores, and subcortical volumes. Then, we performed within-and between-group comparisons with and without controlling for total intracranial volume, age, attention problems, and ADHD problems between SCT and subcortical brain volumes. Finally, we performed correlations between SCT and EF measures for both groups.
Results:Compared to controls, participants with PAE showed significantly more SCT symptoms on the CBCL (t [57] = 3.66, p = 0.0006), more parent-rated attention problems and ADHD symptoms, lower scores across several EF measures (DKEFS Trail-Making and Verbal Fluency; WISC-IV Digit Span, Symbol Search, and Coding; effect sizes ranging from 0.44 to 1.16), and smaller regional volumes in the caudate, hippocampus, and posterior areas of the corpus callosum. In the PAE group, a smaller hippocampus was associated with more SCT symptoms (controlling for parent-rated attention problems and ADHD problems, age, and intracranial volume). However, in the control group, a larger mid posterior and posterior corpus callosum were significantly associated with more SCT symptoms (controlling for parent-rated attention problems, intracranial volume, and age; r [24] = 0.499, p = 0.009; r [24] = 0.517, p = 0.007). In terms of executive functioning, children in the PAE group with more SCT symptoms performed worse on letter sequencing of the Trail-Making subtest (controlling attention problems & ADHD symptoms). In comparison, those in the control group with more SCT symptoms performed better on letter sequencing and combined number letter sequencing of the Trail-Making subtest (controlling attention problems).
Conclusions:Findings suggest that children with FASD experience elevated SCT symptoms compared to typically developing controls, which may be associated with worse performance on EF tasks and smaller subcortical volumes (hippocampus) when taking attention difficulties and ADHD symptoms into account. Additional research into the underlying causes and correlates of SCT in FASD could result in improved tailoring of interventions for this population.
A Review and Evaluation of Homology Hypotheses in Echinoderm Paleobiology
- Colin D. Sumrall, Sarah L. Sheffield, Jennifer E. Bauer, Jeffrey R. Thompson, Johnny A. Waters
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- Published online:
- 24 March 2023
- Print publication:
- 13 April 2023
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- Element
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The extraxial-axial theory (EAT) and universal elemental homology (UEH) are often portrayed as mutually exclusive hypotheses of homology within pentaradiate Echinodermata. EAT describes homology upon the echinoderm bauplan, interpreted through early post-metamorphic growth and growth zones, dividing it into axial regions generally associated with elements of the ambulacral system and extraxial regions that are not. UEH describes the detailed construction of the axial skeleton, dividing it into homologous plates and plate series based on symmetry, early growth, and function. These hypotheses are not in conflict; the latter is rooted in refinement of the former. Some interpretive differences arise because many of the morphologies described from eleutherozoan development are difficult to reconcile with Paleozoic forms. Conversely, many elements described for Paleozoic taxa by UEH, such as the peristomial border plates, are absent in eleutherozoans. This Element recommends these two hypotheses be used together to generate a better understanding of homology across Echinodermata.
Prophylactic hypothermia for traumatic brain injury: a quantitative systematic review
- James L. Fox, Erik N. Vu, Mary Doyle-Waters, Jeffrey R. Brubacher, Riyad Abu-Laban, Zengxuan Hu
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 12 / Issue 4 / July 2010
- Published online by Cambridge University Press:
- 21 May 2015, pp. 355-364
- Print publication:
- July 2010
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Introduction:
During the past 7 years, considerable new evidence has accumulated supporting the use of prophylactic hypothermia for traumatic brain injury (TBI). Studies can be divided into 2 broad categories: studies with protocols for cooling for a short, predetermined period (e.g., 24–48 h), and those that cool for longer periods and/or terminate based on the normalization of intracranial pressure (ICP). There have been no systematic reviews of hypothermia for TBI that include this recent new evidence.
Methods:This analysis followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and the QUOROM (quality of reporting of meta-analyses) statement. We developed a comprehensive search strategy to identify all randomized controlled trials (RCTs) comparing therapeutic hypothermia with standard management in TBI patients. We searched Embase, MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, ProceedingsFirst and PapersFirst. Additional relevant articles were identified by hand-searching conference proceedings and bibliographies. All stages of study identification and selection, quality assessment and analysis were conducted according to prospectively defined criteria. Study quality was determined by assessment of each study for the use of allocation concealment and outcome assessment blinding. Studies were divided into 2 a priori–defined subgroups for analysis based on cooling strategy: short term (≤ 48 h), and long term or goal-directed (> 48 h and/or continued until normalization of ICP). Outcomes included mortality and good neurologic outcome (defined as Glasgow Outcome Scale score of 4 or 5). Pooling of primary outcomes was completed using relative risk (RR) and reported with 95% confidence intervals (CIs).
Results:Of 1709 articles, 12 studies with 1327 participants were selected for quantitative analysis. Eight of these studies cooled according to a long-term or goal-directed strategy, and 4 used a short-term strategy. Summary results demonstrated lower mortality (RR 0.73, 95% CI 0.62–0.85) and more common good neurologic outcome (RR 1.52, 95% CI 1.28–1.80). When only short-term cooling studies were analyzed, neither mortality (RR 0.98, 95% CI 0.75–1.30) nor neurologic outcome (RR 1.31, 95% CI 0.94–1.83) were improved. In 8 studies of long-term or goal-directed cooling, mortality was reduced (RR 0.62, 95% CI 0.51–0.76) and good neurologic outcome was more common (RR 1.68, 95% CI 1.44–1.96).
Conclusion:The best available evidence to date supports the use of early prophylactic mild-to-moderate hypothermia in patients with severe TBI (Glasgow Coma Scale score ≤ 8) to decrease mortality and improve rates of good neurologic recovery. This treatment should be commenced as soon as possible after injury (e.g., in the emergency department after computed tomography) regardless of initial ICP, or before ICP is measured. Most studies report using a temperature of 32°–34°C. The maximal benefit occurred with a long-term or goal-directed cooling protocol, in which cooling was continued for at least 72 hours and/or until stable normalization of intracranial pressure for at least 24 hours was achieved. There is large potential for further research on this therapy in prehospital and emergency department settings.
6 - Ecology and conservation of arboreal rodents of western coniferous forests
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- By Winston P. Smith, USDA Forest Service, Pacific Northwest Research Station, Forestry Sciences Laboratory, Juneau, Alaska 99801-8545, USA, Robert G. Anthony, US Geological Survey, Oregon Cooperative Fish and Wildlife Research Unit, Oregon State University, 104 Nash Hall, Corvallis, Oregon 97331-3803, USA, Jeffrey R. Waters, USDA Forest Service, Redwood Sciences Laboratory, 1700 Bayview Drive, Arcata, California 95519, USA, Norris L. Dodd, Arizona Game and Fish Department, PO Box 2326, Pinetop, Arizona 85935-2326, USA, Cynthia J. Zabel, USDA Forest Service, Redwood Sciences Laboratory, 1700 Bayview Drive, Arcata, California 95519, USA
- Edited by Cynthia J. Zabel, Robert G. Anthony, Oregon State University
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- Book:
- Mammal Community Dynamics
- Published online:
- 15 December 2009
- Print publication:
- 18 September 2003, pp 157-206
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Summary
Introduction
Arboreal rodents were selected as a focal group because of their obvious association with forest canopies and relevance to forest management. The close association of arboreal rodents with trees predisposes them to being impacted by timber harvests (Carey 1989, Aubry et al. 2003, Hallett et al. 2003). Trees provide food, thermal and escape cover, shade, moisture and free water, and cavities that provide nest sites and safe refugia from avian and mammalian predators (Carey 1989, Carey et al. 1999, Aubry 2003). Carey (1989) characterized arboreal rodents according to their degree of dependence on trees for various activities and identified the following stand elements as important to their biology: large live trees, large snags, fallen trees, woody debris, multilayered canopy, overstory and understory diversity, and epiphytes. Additionally, he listed stand stability and landscape contiguity as important attributes with dense underbrush, streamsides, rock, and talus as special features (Carey 1989). More recent studies (e.g., Rosenberg and Anthony 1992, Waters and Zabel 1995, Smith and Nichols 2003) provide new information to examine the conclusions of Carey (1989), which serve as useful hypotheses regarding influences of forest management on arboreal rodent populations in western coniferous forests.
We selected species that are reputed late-seral forest habitat specialists or are known to be important prey for the northern spotted owl (Forsman et al. 2001, Hamer et al. 2001), the American marten (Buskirk and Ruggiero 1994, Ben-David et al. 1997), or the northern goshawk (Accipiter gentilis, Lewis 2001).