Genetic and environmental contributions to regional cortical surface area in humans: a magnetic resonance imaging twin study

Cortical surface area measures appear to be functionally relevant and distinct in etiology, development, and behavioral correlates compared with other size characteristics, such as cortical thickness. Little is known about genetic and environmental influences on individual differences in regional surface area in humans. Using a large sample of adult twins, we determined relative contributions of genes and environment on variations in regional cortical surface area as measured by magnetic resonance imaging before and after adjustment for genetic and environmental influences shared with total cortical surface area. We found high heritability for total surface area and, before adjustment, moderate heritability for regional surface areas. Compared with other lobes, heritability was higher for frontal lobe and lower for medial temporal lobe. After adjustment for total surface area, regionally specific genetic influences were substantially reduced, although still significant in most regions. Unlike other lobes, left frontal heritability remained high after adjustment. Thus, global and regionally specific genetic factors both influence cortical surface areas. These findings are broadly consistent with results from animal studies regarding the evolution and development of cortical patterning and may guide future research into specific environmental and genetic determinants of variation among humans in the surface area of particular regions.     

The effect of gelatin-chondroitin sulfate-hyaluronic acid skin substitute on wound healing in SCID mice

Tissue-engineered skin substitutes provided a feasibility to overcome the shortage of skin autograft by culturing keratinocytes and dermal fibroblasts in vitro. In this study, we applied bi-layer gelatin-chondrointin-6-sulfate-hyaluronic acid (gelatin-C6S-HA) biomatrices onto the severe combined immunodeficiency (SCID) mice to evaluate its effect on promoting wound healing. Human foreskin keratinocytes and dermal fibroblasts were cultured with reconstructed skin equivalent (rSE) for 7 days. The rSE was then grafted to the dorsum of SCID mice to evaluate its biocompatibility by histologic and immunohistochemistry analysis. The results showed that human epidermis were well-developed with the expression of differentiated markers and basement membrane-specific proteins at 4 weeks. After implantation, the percentages of skin graft take were satisfactory, while cell-seeded group was better than non-cell-seeded one. The basement membrane proteins including laminin, type IV collagen, type VII collagen, integrin alpha6, and integrin beta4 were all detected at the dermal-epidermal junction, which showed a continuous structure in the 4 weeks after grafting. This bi-layer gelatin-C6S-HA skin substitute not only has positive effect on promoting wound healing, but also has high rate of graft take. This rSE would have the potential to be applied on the extensively and deeply burned patients who suffer from severe skin defect in the near future.     

Selective dendritic degeneration of medium spiny neurons in dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common form of dementia and shows more severely impaired performance on tests of executive functions compared to Alzheimer disease. Here the authors demonstrate selective spinodendritic degeneration of medium spiny neurons in regions of the caudate nucleus that subserve executive functions and propose that this may underlie, at least in part, the heightened executive dysfunction observed in patients with DLB.     

Retaining intradiscal pressure after annulotomy by different annular suture techniques, and their biomechanical evaluations

Background

The adverse effects of annulotomy during lumbar discectomy have been increasingly recognized, and methods are developing to repair the annular defect. Biomechanically, the repair should retain the intra-nuclear pressure, which is doubtful using the current suture techniques. Therefore, a new suture technique was designed and tested to close a simpler type of annular incision.

Methods

A new suture technique, the modified purse-string suture, was introduced into a re-validated nonlinear finite element human disk model after creating a standard transverse slit incision, as well as two other suture techniques: either two simple sutures, or a horizontal crossed suture, and compared their contact pressure on the cleft contact surface. Then, porcine lumbar endplate–disk–endplate complexes with transverse slit incisions were repaired using the three techniques. Quantitative discomanometry was then applied to compare their leakage pressure, as a parameter of disk integrity.

Findings

In finite element model, the new technique created the greatest contact pressure along the suture range (the outer annulus), and generated a minimum contact pressure at the critical point, which was 68% and 55% higher than the other two suture techniques. In quantitative discomanometry, the new suture technique also had an average leakage pressure of 85% and 49% higher than the other two suture techniques.

Interpretation

The modified purse-string suture can generate higher contact pressure than the other two techniques at finite element analysis and in realistic animal models, which aids in retaining intra-discal pressure, and should be encouraged in clinical practice.     

Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: a preliminary study

Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non-emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age-related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning.