Brain-wide functional connectome analysis of 40,000 individuals reveals brain networks that show aging effects in older adults.

The functional connectome changes with aging. We systematically evaluated aging related alterations in the functional connectome using a whole-brain connectome network analysis in 39,675 participants in UK Biobank project. We used adaptive dense network discovery tools to identify networks directly associated with aging from resting-state fMRI data. We replicated our findings in 499 participants from the Lifespan Human Connectome Project in Aging study. The results consistently revealed two motor-related subnetworks (both permutation test p-values <0.001) that showed a decline in resting-state functional connectivity (rsFC) with increasing age. The first network primarily comprises sensorimotor and dorsal/ventral attention regions from precentral gyrus, postcentral gyrus, superior temporal gyrus, and insular gyrus, while the second network is exclusively composed of basal ganglia regions, namely the caudate, putamen, and globus pallidus. Path analysis indicates that white matter fractional anisotropy mediates 19.6% (p<0.001, 95% CI [7.6% 36.0%]) and 11.5% (p<0.001, 95% CI [6.3% 17.0%]) of the age-related decrease in both networks, respectively. The total volume of white matter hyperintensity mediates 32.1% (p<0.001, 95% CI [16.8% 53.0%]) of the aging-related effect on rsFC in the first subnetwork.

Pathological claustrum activity drives aberrant cognitive network processing in human chronic pain.

Aberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants. Moreover, we discover pathological activity of the claustrum and a region near the posterior inferior frontal sulcus of the right dorsolateral prefrontal cortex (piDLPFC) in migraine patients during acute pain and cognitive task performance. Dynamic causal modeling suggests a directional influence of the claustrum on activity in this piDLPFC region, and diffusion weighted imaging verifies their structural connectivity. These findings advance understanding of claustrum function during acute pain and provide evidence of a possible circuit mechanism driving cognitive impairments in chronic pain.

Pathological claustrum activity drives aberrant cognitive network processing in human chronic pain.

Aberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants. Moreover, we discover pathological activity of the claustrum and a lateral aspect of the right dorsolateral prefrontal cortex (latDLPFC) in migraine patients. Dynamic causal modeling suggests a directional influence of the claustrum on activity in this latDLPFC region, and diffusion weighted imaging (DWI) verifies their structural connectivity. These findings advance understanding of claustrum function during acute pain and provide evidence of a possible circuit mechanism driving cognitive impairments in chronic pain.

Modeling multivariate age-related imaging variables with dependencies.

Neuroimaging techniques have been increasingly used to understand the neural biology of aging brains. The neuroimaging variables from distinct brain locations and modalities can exhibit age-related patterns that reflect localized neural decline. However, it is a challenge to identify the impacts of risk factors (eg, mental disorders) on multivariate imaging variables while simultaneously accounting for the dependence structure and nonlinear age trajectories using existing tools. We propose a mixed-effects model to address this challenge by building random effects based on the latent brain aging status. We develop computationally efficient algorithms to estimate the parameters of new random effects. The simulations show that our approach provides accurate parameter estimates, improves the inference efficiency, and reduces the root mean square error compared to existing methods. We further apply this method to the UK Biobank data to investigate the effects of tobacco smoking on the white matter integrity of the entire brain during aging and identify the adverse effects on white matter integrity with multiple fiber tracts.

Enhancing Light Absorption and Prolonging Charge Separation in Carbon Quantum Dots via Cl-Doping for Visible-Light-Driven Photocharge-Transfer Reactions.

Limited light absorption beyond the UV region and rapid photocarrier recombination are critical impediments for the improved photocatalytic performance of carbon quantum dots (CQDs) under visible-light irradiation. Herein, we demonstrate single-step microwave-assisted syntheses of O-CQDs (typical CQDs terminated by carboxylic and hydroxyl functional groups) from a sucrose precursor and Cl-doped CQDs (Cl-CQDs) from a sucralose precursor in short reaction times and without using obligatory strong acids for Cl doping. The doping of Cl into the CQDs is observed to widen the absorption range and facilitate an enhanced separation of photoexcited charge carriers, which is confirmed by the results of optical absorption, photothermal response, and pump-probe ultrafast transient absorption spectroscopy measurements of the O-CQDs and Cl-CQDs. The photoexcited charge carriers with their longer lifetimes in Cl-CQDs enabled the quick degradation of methylene blue dye, rapid conversion of Ag+ ions to metallic Ag nanoparticles on the CQD surfaces, and reduction of GO to a well-dispersed rGO through the photoelectron transfer reactions under visible-light irradiation. The facile Cl doping strategy, hybridization of Ag nanoparticles or rGO to CQDs, and the elevated charge separation mechanism would open up new avenues in designing CQD-based materials for futuristic applications.

Reliability of Bi-Axial Ankle Stiffness Measurement in Older Adults.

This study involves measurements of bi-axial ankle stiffness in older adults, where the ankle joint is passively moved along the talocrural and subtalar joints using a custom ankle movement trainer. A total of 15 elderly individuals participated in test-retest reliability measurements of bi-axial ankle stiffness at exactly one-week intervals for validation of the angular displacement in the device. The ankle's range of motion was also compared, along with its stiffness. The kinematic measurements significantly corresponded to results from a marker-based motion capture system (dorsi-/plantar flexion: r = 0.996; inversion/eversion: r = 0.985). Bi-axial ankle stiffness measurements showed significant intra-class correlations (ICCs) between the two visits for all ankle movements at slower (2.14°/s, ICC = 0.712) and faster (9.77°/s, ICC = 0.879) speeds. Stiffness measurements along the talocrural joint were thus shown to have significant negative correlation with active ankle range of motion (r = -0.631, p = 0.012). The ankle movement trainer, based on anatomical characteristics, was thus used to demonstrate valid and reliable bi-axial ankle stiffness measurements for movements along the talocrural and subtalar joint axes. Reliable measurements of ankle stiffness may help clinicians and researchers when designing and fabricating ankle-foot orthosis for people with upper-motor neuron disorders, such as stroke.

Effects of passive Bi-axial ankle stretching while walking on uneven terrains in older adults with chronic stroke.

Many people with stroke experience foot drop while walking. Further, walking on uneven surfaces is a common fall risk for these people that hinder with their daily life activities. In addition, a few years after a stroke, lower-limb exercises become less focused, especially the ankle joint movement. The objective of this study is to determine the gait performance of older adults with chronic stroke on an uneven surface in relation to ankle mobility after a four-week bi-axial ankle range of motion (ROM) exercise session. Fifteen older adults with chronic post-stroke hemiparesis (N = 15; mean age = 65 years) participated in a total of 12 bi-axial ankle ROM exercises that consisted of three 30-min training sessions per week for four weeks. Basic clinical tests and gait performance in even and uneven surfaces were evaluated before and after training. Participants with chronic post-stroke hemiparesis showed significantly improved ankle functions, decreased ankle stiffness (from 0.140 ±â€¯0.059 to 0.128 ±â€¯0.067 N·m/°; p = 0.025), and increased paretic ankle passive ROMs (dorsiflexion(DF)/plantarflexion(PF): from 27.3 ±â€¯14.7° to 50.6 ±â€¯10.3°, p < 0.001; inversion(INV)/eversion(EV): 21.7 ±â€¯9.7° to 28.6 ±â€¯9.9°; p = 0.033) after training. They exhibited significant improvements in the walking performance over an uneven surface, step kinematics (walking speed 0.257 ±â€¯0.17 to 0.320 ±â€¯0.178 m/s; p = 0.017; step length: 0.214 ±â€¯0.109 to 0.243 ±â€¯0.108 m; p = 0.009), and clinical balance and mobility (Berg balance scale: 47.2 ±â€¯4.7 to 50.1 ±â€¯3.9, p = 0.0001; timed-up and go test: 23.9 ±â€¯10.3 to 20.2 ±â€¯7.0 s, p = 0.0156). This study is the first research to investigate the walking performance on uneven surfaces in the elderly with chronic stroke in relation to the ankle biomechanical property changes.

Rhythmic auditory stimulation using a portable smart device: short-term effects on gait in chronic hemiplegic stroke patients.

[Purpose] The effects of various rhythmic auditory stimulation tempos on stroke gait pattern changes when training patients with a smartphone-based rhythmic auditory stimulation application were investigated. [Subjects and Methods] Fifteen patients with chronic stroke were included. Cadence during comfortable walking was measured (baseline). After the baseline findings were recorded, rhythmic auditory stimulation with five different tempos (i.e., -10%, -5%, 0%, +5%, and +10% change from baseline) was randomly applied. Finally, comfortable walking without rhythmic auditory stimulation was initiated to evaluate gait pattern changes. [Results] As the tempo increased, the spatiotemporal gait parameters of the stroke patients changed significantly. Gait speed, cadence, and gait cycle duration showed the greatest improvement in the +10% rhythmic auditory stimulation condition compared to baseline. After gait training with rhythmic auditory stimulation, gait speed, cadence, stride length, gait cycle duration, and step length of the affected and unaffected sides improved significantly compared to baseline. [Conclusion] Significant changes in the gait pattern of stroke patients were noted for various tempos after training with rhythmic auditory stimulation. These findings could be used to customize rehabilitative gait training for patients who experience stroke with hemiplegia.

Kinematic analysis of upper extremity movement during drinking in hemiplegic subjects.

BACKGROUND: It is necessary to analyze the kinematic properties of a paralyzed extremity to quantitatively determine the degree of impairment of hemiplegic people during functional activities of daily living (ADL) such as a drinking task. This study aimed to identify the kinematic differences between 16 hemiplegic and 32 able-bodied participants in relation to the task phases when drinking with a cup and the kinematic strategy used during motion with respect to the gravity direction. METHODS: The subjects performed a drinking task that was divided into five phases according to Murphy's phase definition: reaching, forward transport, drinking, backward transport, and returning. We found that the groups differed in terms of the movement times and the joint angles and angular velocities of the shoulder, elbow, and wrist joints. FINDINGS: Compared to the control group, the hemiplegic participants had a larger shoulder abduction angle of at most 17.1° during all the phases, a larger shoulder flexion angle of 7.6° during the reaching phase, and a smaller shoulder flexion angle of 6.4° during the backward transporting phase. Because of these shoulder joint patterns, a smaller elbow pronation peak angle of at most 13.1° and a larger wrist extension peak angle of 12.0° were found in the motions of the hemiplegic participants, as compensation to complete the drinking task. The movement in the gravity direction during the backward transporting phase resulted in a 15.9% larger peak angular velocity for elbow extension in the hemiplegic participants compared to that of the control group. INTERPRETATION: These quantitative kinematic patterns help provide an understanding of the movements of an affected extremity and can be useful in designing rehabilitation robots to assist hemiplegic people with ADL.

Synthesis of 1,3-azaphosphol-2-ones. Crystal and molecular structures of [SP-4-2]-dichlorobis(3-phenyl-1,3-dihydrobenzo[1,3]azaphosphol-2-one-P)palladium(II) and its chloro(methyl)platinum(II) analogue.

Reaction of secondary phosphine (+/-)-(2-aminophenyl)phenylphosphine, (+/-)-app, with PCl(5) in toluene gives the hydrochloride salt of the expected chlorophosphine (+/-)-(2-aminophenyl)chlorophenylphosphine, (+/-)-acpp.HCl, however, this is not the case with triphosgene. Rather the first example of a 1,3-azaphosphol-2-one is isolated, viz. (+/-)-3-phenyl-1,3-dihydrobenzo[1,3]azaphosphol-2-one, (+/-)-pbap. The hydrochloride salt (+/-)-acpp.HCl readily reacts with excess vinyl-, 2-methylphenyl- or 2-methoxyphenyl magnesium bromide to give the corresponding tertiary phosphines (+/-)-(2-H(2)NC(6)H(4))PPhR (where R = CH=CH(2), 2-C(6)H(4)Me or 2-C(6)H(4)OMe). Hydrophosphination of the vinyl substituted tertiary phosphine with (+/-)-app in the presence of KOBu(t) provides a synthetic route to the elusive P(2)N(2) quadridentate ligand (R(P)*,R(P)*)- and (R(P)*,S(P)*)-(CH(2))(2)(PPhC(6)H(4)NH(2)-2)(2), albeit in low yield. The azaphospholone (+/-)-pbap can be readily deprotonated with KOBu(t) in thf and subsequently alkylated with methyl iodide or benzyl bromide to give the analogous N-methyl or N-benzyl derivatives. Alkylation with 1,3-dibromopropane gives the bis(azaphospholone) (R(P)*,R(P)*)- and (R(P)*,S(P)*)-1,3-bis[1-{3-phenyl-1,3-dihydrobenzo[1,3]azaphosphol-2-one}]propane. The latter and the N-methyl substituted azaphospholone can also be synthesised by the reaction of the corresponding secondary phosphine, viz. (R(P)*,R(P)*)- and (R(P)*,S(P)*)-(CH(2))(3)(NHC(6)H(4)PHPh-2)(2) and (+/-)-(2-methylaminophenyl)phenylphosphine, with triphosgene. All three azaphospholones react with [PtClMe(1,5-cyclooctadiene)] in thf to give complexes of the type cis-[PtClMeL(2)] in which ligand L is coordinated via the P atom of the azaphospholones. The ligand (+/-)-pbap has also been complexed to palladium(II) via the reaction with Li(2)[PdCl(4)] in methanol to give cis-[PdCl(2){(+/-)-pbap}(2)]. The structures of cis-[PtClMe{(+/-)-pbap}(2)] and cis-[PdCl(2){(+/-)-pbap}(2)] have been confirmed by X-ray analysis.