Metacarpal trabecular bone varies with distinct hand-positions used in hominid locomotion

Trabecular bone remodels during life in response to loading and thus should, at least in part, reflect potential variation in the magnitude, frequency and direction of joint loading across different hominid species. Here we analyse the trabecular structure across all non-pollical metacarpal distal heads (Mc2-5) in extant great apes, expanding on previous volume of interest and whole-epiphysis analyses that have largely focussed on only the first or third metacarpal. Specifically, we employ both a univariate statistical mapping and a multivariate approach to test for both inter-ray and interspecific differences in relative trabecular bone volume fraction (RBV/TV) and degree of anisotropy (DA) in Mc2-5 subchondral trabecular bone. Results demonstrate that while DA values only separate Pongo from African apes (Pan troglodytes, Pan paniscus, Gorilla gorilla), RBV/TV distribution varies with the predicted loading of the metacarpophalangeal (McP) joints during locomotor behaviours in each species. Gorilla exhibits a relatively dorsal distribution of RBV/TV consistent with habitual hyper-extension of the McP joints during knuckle-walking, whereas Pongo has a palmar distribution consistent with flexed McP joints used to grasp arboreal substrates. Both Pan species possess a disto-dorsal distribution of RBV/TV, compatible with multiple hand postures associated with a more varied locomotor regime. Further inter-ray comparisons reveal RBV/TV patterns consistent with varied knuckle-walking postures in Pan species in contrast to higher RBV/TV values toward the midline of the hand in Mc2 and Mc5 of Gorilla, consistent with habitual palm-back knuckle-walking. These patterns of trabecular bone distribution and structure reflect different behavioural signals that could be useful for determining the behaviours of fossil hominins

Resting-state global functional connectivity as a biomarker of cognitive reserve in mild cognitive impairment

Cognitive reserve (CR) shows protective effects in Alzheimer’s disease (AD) and reduces the risk of dementia. Despite the clinical significance of CR, a clinically useful diagnostic biomarker of brain changes underlying CR in AD is not available yet. Our aim was to develop a fully-automated approach applied to fMRI to produce a biomarker associated with CR in subjects at increased risk of AD. We computed resting-state global functional connectivity (GFC), i.e. the average connectivity strength, for each voxel within the cognitive control network, which may sustain CR due to its central role in higher cognitive function. In a training sample including 43 mild cognitive impairment (MCI) subjects and 24 healthy controls (HC), we found that MCI subjects with high CR (> median of years of education, CR+) showed increased frequency of high GFC values compared to MCI-CR- and HC. A summary index capturing such a surplus frequency of high GFC was computed (called GFC reserve (GFC-R) index). GFC-R discriminated MCI-CR+ vs. MCI-CR-, with the area under the ROC = 0.84. Cross-validation in an independently recruited test sample of 23 MCI subjects showed that higher levels of the GFC-R index predicted higher years of education and an alternative questionnaire-based proxy of CR, controlled for memory performance, gray matter of the cognitive control network, white matter hyperintensities, age, and gender. In conclusion, the GFC-R index that captures GFC changes within the cognitive control network provides a biomarker candidate of functional brain changes of CR in patients at increased risk of AD

Novel variants identified in methyl-CpG-binding domain genes in autistic individuals

Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome. We hypothesized that mutations in other members of the methyl-CpG-binding domain (MBD) family may also cause autistic features in individuals. We evaluated 226 autistic individuals for alterations in the four genes most homologous to MECP2: MBD1, MBD2, MBD3, and MBD4. A total of 46 alterations were identified in the four genes, including ten missense changes and two deletions that alter coding sequence. Several are either unique to our autistic population or cosegregate with affected individuals within a family, suggesting a possible relation of these variations to disease etiology. Variants include a R23M alteration in two affected half brothers which falls within the MBD domain of the MBD3 protein, as well as a frameshift in MBD4 that is predicted to truncate almost half of the protein. These results suggest that rare cases of autism may be influenced by mutations in members of the dynamic MBD protein family