Greater age-related changes in white matter morphometry following early life stress: Associations with internalizing problems in adolescence

Early life stress (ELS) is associated with increased risk for internalizing disorders and variations in gray matter development. It is unclear, however, whether ELS affects normative age-related changes in white matter (WM) morphology, and if such maturational differences are associated with risk for internalizing psychopathology. We conducted comprehensive interviews in a cross-sectional sample of young adolescents (N = 156; 89 F; Ages 9–14) to assess lifetime exposure to stress and objective cumulative ELS severity. We used diffusion-weighted imaging to measure WM fixel-based morphometry and tested the effects of age and ELS on WM fiber density and cross-section (FDC), and associations between WM FDC and internalizing problems. Age was positively associated with FDC in all WM tracts; greater ELS severity was related to stronger age-WM associations in several association tracts connecting the frontal lobes with limbic, parietal, and occipital regions, including bilateral superior and inferior longitudinal and uncinate fasciculi (UF). Among older adolescents with greater ELS severity, a higher UF FDC was associated with fewer internalizing problems. Greater ELS severity predicted more mature WM morphometry in tracts implicated in emotion regulation and cognitive processing. More phenotypically mature UF WM may be adaptive against internalizing psychopathology in adolescents exposed to ELS.     

The effects of puberty on white matter development in boys

Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD) and fractional anisotropy (FA) in 61 males aged 12.7–16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n = 22) and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n = 39). Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol) were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty × age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone.     

Foam film stratification studies probe intermicellar interactions

Ultrathin foam films containing supramolecular structures like micelles in bulk and adsorbed surfactant at the liquid–air interface undergo drainage via stratification. At a fixed surfactant concentration, the stepwise decrease in the average film thickness of a stratifying micellar film yields a characteristic step size that also describes the quantized thickness difference between coexisting thick–thin flat regions. Even though many published studies claim that step size equals intermicellar distance obtained using scattering from bulk solutions, we found no reports of a direct comparison between the two length scales. It is well established that step size is inversely proportional to the cubic root of surfactant concentration but cannot be estimated by adding micelle size to Debye length, as the latter is inversely proportional to the square root of surfactant concentration. In this contribution, we contrast the step size obtained from analysis of nanoscopic thickness variations and transitions in stratifying foam films using Interferometry Digital Imaging Optical Microscopy (IDIOM) protocols, that we developed, with the intermicellar distance obtained using small-angle X-ray scattering. We find that stratification driven by the confinement-induced layering of micelles within the liquid–air interfaces of a foam film provides a sensitive probe of non-DLVO (Derjaguin–Landau–Verwey–Overbeek) supramolecular oscillatory structural forces and micellar interactions.

Molecules in simple liquids and supramolecular structures in complex fluids can stratify or undergo confinement-induced layering induced by symmetry breaking at a solid–liquid or a fluid–fluid interface (1–8). In freestanding or foam films, the confinement-induced layering of supramolecular structures including micelles (9–17), lipid layers (18, 19), polyelectrolyte–surfactant complexes (20, 21), nanoparticles (9, 22), and liquid crystalline assemblies (23) can result in drainage via stratification. Due to thin film interference, foam films visualized under white light illumination display iridescent colors for thick films (h > 100 nm) (24–28), but ultrathin films (h < 100 nm) exhibit shades of gray that get progressively darker as the film gets thinner (9–21). In reflected light microscopy, micellar foam films exhibit coexisting thick−thin regions with distinct shades of gray. Interferometry-based measurement of the average film thickness over time decreases in a stepwise fashion yielding a step size, Δh (9–17). Many published studies argue (9–12, 22, 29–34) that foam films containing charged micelles or latex particles stratify analogously due to the formation of “ordered colloidal crystals” (OCCs) and step size, Δh, equals the intermicellar distance, d, in bulk solutions. However, a comparison of concentration-dependent Δh obtained from the dynamic foam stratification studies (influenced by confinement effects) with d measured using small-angle X-ray or neutron scattering (SAXS or SANS) or other direct measurements of static equilibrium structure, and related evidence for or against the formation of OCCs in micellar foam films, are lacking in the literature. Thus, the motivations of this contribution are threefold: 1) contrast the step size, Δh, obtained via stratification studies with the intermicellar distance, d, and micelle dimensions determined using SAXS; 2) examine the SAXS data for any evidence of OCCs; and 3) elucidate the influence of ionic micelles on foam film stability and topography, as well as on colloidal forces, in multicomponent complex fluids.Micelles, formed by self-assembly of soaps and detergents and ever present in typical household foams, facilitate cleaning and detergent action by solubilizing oils and oil-soluble dirt within their hydrophobic core (2, 34, 35). Micelles formed by biosurfactants like bile salt and rhamnolipids can be used for delivering nonpolar, bio-active polyunsaturated oils, flavonoids, vitamins, and hydrophobic drugs (36–38). Therefore, understanding the stability and lifetime of micellar foams is essential toward molecular engineering of formulations, controlling foams in industrial reactors, rivers, and lakes and developing bio-surfactants (36–38). Foam film drainage involves interfacial flows that are influenced both by bulk rheology and interfacial rheology as well as Laplace or capillary pressure, Pc=σC (set by surface tension, σ and curvature, C) (27, 28, 39–41). Additionally, thickness transitions and variations in ultrathin (h < 100 nm) freestanding as well as supported (containing one or two solid boundaries) films (41–43) depend on disjoining pressure, Π(h)=−(∂G/∂h)P,T,A,Ni, defined as the free energy required to change unit thickness at constant temperature, T, pressure, P, surface area, A, and mole number, N_i (1, 34, 40–42). Intermolecular and surface forces determine the strength and range of disjoining pressure, Π(h), as well as of colloidal interaction forces, F(h) (1–3, 35, 40–42). Physical properties of surfactant solutions like surface tension and conductivity show distinct change around a critical micelle concentration (CMC), beyond which spheroidal micelles can form (2, 34, 35), and rod-like micelles, lamellar phases, etc., emerge at higher concentrations (44–46). In foam films formed with ionic surfactant at c < CMC, drainage below h < 30 nm often leads to the formation of relatively long-lived common black (CB) film attributed to counterbalancing of P_c by ΠDLVO(h), the disjoining pressure due to DLVO (Derjaguin–Landau–Verwey–Overbeek) forces contributed by van der Waals and electrostatic double-layer interactions (1–3, 35, 39, 40). Even thinner Newton black (NB) films attest to the role of shorter-range, non-DLVO surface forces (14, 25–27, 40, 41). In contrast, in micellar foam films (c > CMC), a non-DLVO, oscillatory structural force, ΠOS(h), counterbalances P_c at multiple flat thicknesses, manifested as distinct shades of gray in reflected light microscopy (9–17, 21, 40, 47–50).For micellar fluids containing charged micelles, the step size, Δh, obtained using thickness–time plots from stratification experiments, and periodicity, λ, of ΠOS(h) directly measured using thin-film balance (47, 48) show that both periodicity and step size exceed micelle size, a, implying λ>a and Δh>a. In 1971, Bruil and Lyklema (51) were the first to report that the concentration-dependent decrease in step size measured for sodium dodecyl sulfate (SDS) solutions followed a power law of the form Δh∝csoap−1/3 and wrote that step size values “seem to be related to intermolecular distance in the (unmicellized) bulk solution.” In 1988, Nikolov et al. (9) reported that foam films containing latex particles stratified in a fashion similar to micellar foam films and argued that diffusion-driven, layer-by-layer removal of micelles or particles from an ordered colloidal crystal (OCC) structure drives stratification. In their OCC or “micelle-vacancy diffusion” mechanism, they proposed that the effective film viscosity increases with decrease in stratified film thickness (9, 10, 29–31, 33). Contrastingly, in the “hydrodynamic” mechanism, Bergeron and Radke (13, 47) described stratification using a thin-film equation, by incorporating ΠOS(h) and bulk solution viscosity. Nikolov et al. (9, 10, 29–31) suggested that the step size, Δh, was equal to an effective diameter, deff=2lSDS+κ−1, computed by adding the fixed length of SDS molecules, l_SDS, to the Debye length, κ−1, that captures the range of screened electrostatic interactions. However, the step size Δh∼c−1/3 and the Debye length κ−1∼c−1/2 display distinct power laws, and the measured step size exceeds the micelle size, a, as well as the computed effective diameter, d_eff, for ionic micellar systems, or typically Δh>a and Δh>deff.Studies on charged nanoparticle dispersions find that the periodicity, λ, of the oscillatory structural force, F(h), measured directly with surface force apparatus (SFA), or colloidal probe atomic force microscopy (CP-AFM), correlates well with the interparticle distance, d, obtained using scattering and simulations (4, 5, 52–55). Furthermore, the periodicity, λ≈d≫a, is primarily set by the particle number density, ρ, and is relatively independent of added salt, charge at solid surfaces, and particle size, a (4, 5, 53–55). Assuming that analogy between λ∝ρ−1/3 in the nanoparticle studies and Δh∝c−1/3 in stratified foam studies arises due to similar underlying physics, Danov et al. (32) and Anachkov et al. (11) argued that Δh≈d or step size equals the intermicellar distance, d, in bulk solutions and hypothesized that step size from stratification studies could be used for determining aggregation number as Nagg≈(c−CMC)(Δh)3. However, Yilixiati et al. (17) showed that on salt addition, the measured Δh values for micellar SDS solutions do not collapse onto a single curve even if plotted against micellar number density, ρ, as micelle number and dimensions can change on the addition of salt (or surfactant) (2), whereas nanoparticle dimensions remain constant. Furthermore, solid boundaries that can impact SFA and AFM measurements are absent in stratifying foam films. However, the thickness of stratifying films is rather heterogeneous, and the average thickness changes in a stepwise fashion. Thus, the analogy between stratifying micelles in foam films and stratifying nanoparticle dispersions under confinement between solid surfaces requires further investigation. In particular, a comparison between multiple length-scales including micelle dimensions, Debye length, intermicellar distance, d and step-size, Δh, and the consequences of thickness heterogeneities within foam films are warranted.In this study, we contrast the concentration-dependent changes in step-size measured in foam stratification studies with micellar dimensions and intermicellar distances in bulk solutions obtained using SAXS for aqueous solutions of SDS. For the range of concentrations (25 mM ≤ c_SDS ≤ 250 mM) explored here, bulk rheology, interfacial tension, micelle shape and size, and interfacial charge (or potential) are nearly constant. Hence, the observed concentration-dependent changes in step-size and nanoscopic topography in stratifying films are dictated by the corresponding changes in intermicellar interactions and the resulting disjoining pressure, ΠOS(h). We visualize and analyze nanoscopic thickness variations and transitions in stratifying foam films using IDIOM (Interferometry Digital Imaging Optical Microscopy) protocols (16) (Fig. 1A) that provide requisite spatiotemporal resolution (thickness ∼1 nm, in-plane < 1 μm, time < 1 ms). We analyze SAXS data to compute micelle dimensions, volume fraction, and microstructure (order) in bulk solutions and obtain the intermicellar distance from structure factor peak in SAXS data. Finally, we discuss the ramifications of the close comparison between step size from the foam film stratification studies and micellar dimensions and intermicellar distance determined using SAXS analysis on the intermicellar interactions and the mechanistic basis of stratification.Open in a separate windowFig. 1.Schematic of the setup used for examining stratification using IDIOM protocols and illustrative examples of stepwise thinning. (A) The Scheludko-like cell contains a plane-parallel film and surrounding meniscus that emulates a single foam film and its Plateau border. The cell is placed in a closed container and stratification is visualized using reflected light microscopy. A finite volume of fluid is inserted into the cell using the side-arm connected to a syringe. No liquid is added or withdrawn during the stratification experiment, and drainage from the film into the meniscus occurs freely and spontaneously. (B) Spatiotemporal variation in interference intensity I(x, y, t; λ) is used for computing thickness transitions and variations in stratifying films. (C) Average film thickness plotted as a function of time shows stepwise thinning for foam films made with aqueous SDS solutions. The spikes and dips in thickness plots appear when mesas or domains emerge in the region selected for computing average thickness. The data are shifted horizontally for clarity.     

Ultrasound Diagnosis of Carotid Artery Stiffness in Patients with Ischemic Leukoaraiosis

The pathophysiology of ischemic leukoaraiosis (ILA) is unknown. It was recently found that ILA patients have increased aortic stiffness. Carotid stiffness is a more specific parameter and could have value as a non-invasive diagnostic value for ILA. Therefore, using color-coded duplex sonography, we compared local carotid stiffness parameters of 59 patients with ILA with those of 45 well-matched controls. The diagnosis of ILA was based on exclusion of other causes of white matter changes seen on magnetic resonance imaging. Pulse wave velocity β (PWVβ, m/s), pressure–strain elasticity modulus (E_p, kPa), β index and augmentation index (A_ix, %) values were higher and arterial compliance (AC, mm²/kPa) values were lower in the ILA group; however, only E_p and PWVβ reached statistical significance (p ≤ 0.05). β, E_p and PWVβ exhibited an increasing trend with higher Fazekas score, though only E_p reached significance (p = 0.05). The main conclusion was that E_p and PWVβ could have a diagnostic role in patients with ILA.     

弥散峰度成像评估阿尔茨海默病脑部白质纤维束损害

目的 探讨弥散峰度成像(DKI)对于阿尔茨海默病(AD)的诊断价值。方法 对19例AD患者(AD组)和17名健康体检者(对照组)行DKI扫描,测量并比较两组胼胝体膝部、胼胝体压部、双侧前扣带束、双侧后扣带束、双侧上纵束和双侧下枕额束的弥散张量成像(DTI)和DKI参数值,分析各参数与简易精神状态检查量表(MMSE)评分的相关性。结果 AD组胼胝体膝部、压部,双侧前扣带束,双侧后扣带束的各向异性分数(FA)、平均扩散程度(MD)、径向扩散程度(RD)和平均弥散峰度(MK)、径向峰度(RK)、轴向峰度(AK),双侧上纵束和双侧下枕额束MK、RK、AK值与对照组的差异均有统计学意义(P均<0.05);AD组同一患者右前扣带束的FA、MK、AK、RK值,右后扣带束FA值,左上纵束FA、RD、MK、RK值与右侧的差异均有统计学意义(P均<0.05);DTI和DKI参数值与MMSE均具有相关性,胼胝体膝部MK值与MMSE的相关性最高(r=0.55,P<0.05)。结论 DKI可敏感、准确地评价认知障碍的严重程度。     

基于体素的形态学MRI观察未经药物治疗的强迫症患者脑灰质结构改变

目的 探查未经药物治疗的强迫症患者脑灰质结构存在异常的区域,并探讨脑灰质体积改变与临床症状之间的关系.方法 用基于体素的形态学方法(voxel-based morphometry,VBM),对比分析21例未经药物治疗的强迫症患者和21例年龄、性别及受教育程度相匹配的正常对照者脑灰质体积存在差异的脑区,并采用耶鲁-布郎量表(Y-BOCS)、汉密尔顿抑郁量表(HAMD)及汉密尔顿焦虑量表(HAMA)评估临床症状.结果 强迫症患者与正常对照者相比脑灰质结构存在明显萎缩的区域主要位于双侧眶额叶、前扣带回、右侧丘脑以及右侧小脑(P＜0.05,FDR校正),患者左侧眶额叶的灰质体积与耶鲁布朗量表评分之间存在负相关(r=-0.63,P＜0.01).结论“皮质-纹状体-丘脑-皮质”环路的结构异常在强迫症的发病机制中起着重要作用,同时表明环路外小脑等结构的异常也可能参与了强迫症的病理生理学进程.