Subregional Hippocampal Thickness Abnormalities in Older Adults with a History of Heavy Cannabis Use.

Background and Aims: Legalization of cannabis (CB) for both medicinal and, in some states, recreational use, has given rise to increasing usage rates across the country. Of particular concern are indications that frequent CB use may be selectively harmful to the developing adolescent brain compared with adult-onset usage. However, the long-term effects of heavy, adolescent CB use on brain structure and cognitive performance in late-life remain unknown. A critical brain region is the hippocampus (HC), where there is a striking intersection between high concentrations of cannabinoid 1 (CB1) receptors and age-related pathology. Design: We investigated whether older adults (average age=66.6+7.2 years old) with a history of early life CB use show morphological differences in hippocampal subregions compared with older, nonusers. Methods: We performed high-resolution magnetic resonance imaging combined with computational techniques to assess cortical thickness of the medial temporal lobe, neuropsychological testing, and extensive drug use histories on 50 subjects (24 formerly heavy cannabis users [CB+ group] abstinent for an average of 28.7 years, 26 nonusers [CB- group]). We investigated group differences in hippocampal subregions, controlling for age, sex, and intelligence (as measured by the Wechsler Test of Adult Reading), years of education, and cigarette use. Results: The CB+ subjects exhibited thinner cortices in subfields cornu ammonis 1 [CA1; F(1,42)=9.96, p=0.0003], and CA2, 3, and the dentate gyrus [CA23DG; F(1,42)=23.17, p<0.0001], and in the entire HC averaged over all subregions [F(1,42)=8.49, p=0.006]. Conclusions: Negative effects of chronic adolescent CB use on hippocampal structure are maintained well into late life. Because hippocampal cortical loss underlies and exacerbates age-related cognitive decline, these findings have profound implications for aging adults with a history of early life usage. Clinical Trial Registration: ClinicalTrials.gov # NCT01874886

Physical Activity and Hippocampal Sub-Region Structure in Older Adults with Memory Complaints.

BackgroundPhysical activity (PA) plays a major role in maintaining cognition in older adults. PA has been shown to be correlated with total hippocampal volume, a memory-critical region within the medial temporal lobe (MTL). However, research on associations between PA and MTL sub-region integrity is limited.ObjectiveTo examine the relationship between PA, MTL thickness, and its sub-regions, and cognitive function in non-demented older adults with memory complaints.MethodsTwenty-nine subjects aged ≥60 years, with memory complaints were recruited for this cross-sectional study. PA was tracked for 7 days using accelerometers, and average number of steps/day determined. Subjects were categorized into two groups: those who walked ≤4000 steps/day (lower PA) and those with >4000 steps/day (higher PA). Subjects received neuropsychological testing and 3T MRI scans. Nonparametric ANCOVAs controlling for age examined differences between the two groups.ResultsTwenty-six subjects aged 72.7(8.1) years completed the study. The higher PA group (n = 13) had thicker fusiform gyrus (median difference = 0.11 mm, effect size (ES) = 1.43, p = 0.001) and parahippocampal cortex (median difference = 0.12 mm, ES = 0.93, p = 0.04) compared to the lower PA group. The higher PA group also exhibited superior performance in attention and information-processing speed (median difference = 0.90, ES = 1.61, p = 0.003) and executive functioning (median difference = 0.97, ES = 1.24, p = 0.05). Memory recall was not significantly different between the two groups.ConclusionOlder non-demented individuals complaining of memory loss who walked >4000 steps each day had thicker MTL sub-regions and better cognitive functioning than those who walked ≤4000 steps. Future studies should include longitudinal analyses and explore mechanisms mediating hippocampal related atrophy

Thickness in Entorhinal and Subicular Cortex Predicts Episodic Memory Decline in Mild Cognitive Impairment

Identifying subjects with mild cognitive impairment (MCI) most likely to decline in cognition over time is a major focus in Alzheimer's disease (AD) research. Neuroimaging biomarkers that predict decline would have great potential for increasing the efficacy of early intervention. In this study, we used high-resolution MRI, combined with a cortical unfolding technique to increase visibility of the convoluted medial temporal lobe (MTL), to assess whether gray matter thickness in subjects with MCI correlated to decline in cognition over two years. We found that thickness in the entorhinal (ERC) and subicular (Sub) cortices of MCI subjects at initial assessment correlated to change in memory encoding over two years (ERC: r = 0.34; P = .003) and Sub (r = 0.26; P = .011) but not delayed recall performance. Our findings suggest that aspects of memory performance may be differentially affected in the early stages of AD. Given the MTL's involvement in early stages of neurodegeneration in AD, clarifying the relationship of these brain regions and the link to resultant cognitive decline is critical in understanding disease progression

Cardiovascular Dynamics in Crocodylus porosus Breathing Air and During Voluntary Aerobic Dives

Pressure records from the heart and outflow vessels of the heart of Crocodylus porosus resolve previously conflicting results, showing that left aortic filling via the foramen of Panizza may occur during both cardiac diastole and systole. Filling of the left aorta during diastole, identified by the asynchrony and comparative shape of pressure events in the left and right aortae, is reconciled more easily with the anatomy, which suggests that the foramen would be occluded by opening of the pocket valves at the base of the right aorta during systole. Filling during systole, indicated when pressure traces in the left and right aortae could be superimposed, was associated with lower systemic pressures, which may occur at the end of a voluntary aerobic dive or can be induced by lowering water temperature or during a long forced dive. To explain this flexibility, we propose that the foramen of Panizza is of variable calibre. The presence of a 'right-left' shunt, in which increased right ventricular pressure leads to blood being diverted from the lungs and exiting the right ventricle via the left aorta, was found to be a frequent though not obligate correlate of voluntary aerobic dives. This contrasts with the previous concept of the shunt as a correlate of diving bradycardia. The magnitude of the shunt is difficult to assess but is likely to be relatively small. This information has allowed some new insights into the functional significance of the complex anatomy of the crocodilian heart and major blood vessels

Effects of Land Crabs on Leaf Litter Distributions and Accumulations in a Mainland Tropical Rain Forest 1

The effect of the fossorial land crab Gecarcinus quadratus (Gecarcinidae) on patterns of accumulation and distribution of leaf litter was studied for two years in the coastal primary forests of Costa Rica's Corcovado National Park. Within this mainland forest, G, quadratus achieve densities up to 6 crabs/m 2 in populations extending along the Park's Pacific coastline and inland for ca 600 m. Crabs selectively forage for fallen leaf litter and relocate what they collect to burrow chambers that extend from 15 to 150 cm deep ( N = 44), averaging (±SE) 48.9 ± 3.0 cm. Preference trials suggested that leaf choice by crabs may be species-specific. Excavated crab burrows revealed maximum leaf collections of 11.75 g dry mass– 2.5 times more leaf litter than collected by square-meter leaf fall traps over several seven-day sampling periods. Additionally, experimental crab exclosures (25 m 2 ) were established using a repeated measures randomized block design to test for changes in leaf litter as a function of reduced crab density. Exclosures accumulated significantly more (5.6 ± 3.9 times) leaf litter than did control treatments during the wet, but not the dry, seasons over this two-year study. Such extensive litter relocation by land crabs may affect profiles of soil organic carbon, rooting, and seedling distributions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73250/1/j.1744-7429.2003.tb00590.x.pd

Abiotic conditions in cephalopod (Sepia officinalis) eggs: embryonic development at low pH and high pCO2

Low pO(2) values have been measured in the perivitelline fluids (PVF) of marine animal eggs on several occasions, especially towards the end of development, when embryonic oxygen consumption is at its peak and the egg case acts as a massive barrier to diffusion. Several authors have therefore suggested that oxygen availability is the key factor leading to hatching. However, there have been no measurements of PVF pCO(2) so far. This is surprising, as elevated pCO(2) could also constitute a major abiotic stressor for the developing embryo. As a first attempt to fill this gap in knowledge, we measured pO(2), pCO(2) and pH in the PVF of late cephalopod (Sepia officinalis) eggs. We found linear relationships between embryo wet mass and pO(2), pCO(2) and pH. pO(2) declined from > 12 kPa to less than 5 kPa, while pCO(2) increased from 0.13 to 0.41 kPa. In the absence of active accumulation of bicarbonate in the PVF, pH decreased from 7.7 to 7.2. Our study supports the idea that oxygen becomes limiting in cephalopod eggs towards the end of development; however, pCO(2) and pH shift to levels that have caused significant physiological disturbances in other marine ectothermic animals. Future research needs to address the physiological adaptations that enable the embryo to cope with the adverse abiotic conditions in their egg environment

The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

Deep clinical and biological phenotyping of the preterm birth and small for gestational age syndromes: The INTERBIO-21 st Newborn Case-Control Study protocol.

Background: INTERBIO-21 st is Phase II of the INTERGROWTH-21 st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21 st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment

Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism

People with the apolipoprotein-Eε4 (APOE-4) genetic risk for Alzheimer's disease show morphologic differences in medial temporal lobe regions when compared to non-carriers of the allele. Using a high-resolution MRI and cortical unfolding approach, our aim was to determine the rate of cortical thinning among medial temporal lobe subregions over the course of 2 years. We hypothesized that APOE-4 genetic risk would contribute to longitudinal cortical thickness change in the subiculum and entorhinal cortex, regions preferentially susceptible to Alzheimer's disease related pathology. Thirty-two cognitively intact subjects, mean age 61 years, 16 APOE-4 carriers, 16 non-carriers, underwent baseline and follow-up MRI scans. Over this relatively brief interval, we found significantly greater cortical thinning in the subiculum and entorhinal cortex of APOE-4 carriers when compared to non-carriers of the allele. Average cortical thinning across all medial temporal lobe subregions combined was also significantly greater for APOE-4 carriers. This finding is consistent with the hypothesis that carrying the APOE-4 allele renders subjects at a higher risk for developing Alzheimer's disease