Efficacy and Safety of High-Dose TBS on Post-Stroke Upper Extremity Motor Impairment: A Randomized Controlled Trial.

BACKGROUND: Upper extremity (UE) motor function impairment is a major poststroke complication whose recovery remains one of the most challenging tasks in neurological rehabilitation. This study examined the efficacy and safety of the personalized neuroimaging-guided high-dose theta-burst stimulation (TBS) for poststroke UE motor function recovery. METHODS: Patients after stroke with UE motor impairment from a China rehabilitation center were randomly assigned to receive high-dose intermittent TBS (iTBS) to ipsilesional UE sensorimotor network, continuous TBS (cTBS) to contralesional UE sensorimotor network, or sham stimulation, along with conventional therapy for 3 weeks. The primary outcome was the score changes on the Fugl-Meyer assessment-UE from baseline to 1 and 3 weeks. The secondary outcomes included the response rate on Fugl-Meyer assessment-UE scores posttreatment (≥9-point improvement) and score changes in multidimensional scales measuring UE, lower extremity, and activities and participation. RESULTS: From June 2021 to June 2022, 45 participants were randomized and 43 were analyzed. The iTBS and continuous TBS groups showed significantly greater improvement in Fugl-Meyer assessment-UE (mean improvement, iTBS: 10.73 points; continuous TBS: 10.79 points) than the sham group (2.43 points) and exhibited significantly greater response rates on Fugl-Meyer assessment-UE (iTBS, 60.0%; continuous TBS, 64.3%) than the sham group (0.0%). The active groups consistently exhibited superior improvement on the other 2 UE assessments at week 3. However, only the iTBS group showed greater efficacy on 1 lower extremity assessment than the sham group at week 3. Both active groups showed significant improvements in activities and participation assessments. CONCLUSIONS: The study provides evidence for the efficacy and safety of high-dose TBS in facilitating poststroke UE rehabilitation. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2100047340.

Functional connectivity of the auditory cortex in women with trauma-related disorders who hear voices.

BACKGROUND: 'Voice-hearing' (VH) is a transdiagnostic experience that is common in trauma-related disorders (trauma-D). However, the neural substrates underlying trauma-related VH remain largely unexplored. While auditory perceptual dysfunction is among the abnormalities implicated in schizophrenia VH, whether VH in trauma-D also involves auditory perceptual alterations is unknown. METHODS: We investigated auditory cortex (AC)-related functional connectivity (FC) in n=65 women with trauma-D related to childhood abuse with varying severities of VH. Using a novel, computationally-driven and individual-specific method of functionally parcellating the brain, we calculated the FC of two distinct AC subregions-Heschl's gyrus (HG, corresponding to primary AC) and lateral superior temporal gyrus (lSTG, in non-primary AC)- with both the cerebrum and cerebellum. We then measured the association between VH severity and FC using leave-one-out cross validation within the cerebrum, and voxel-wise multiple regression analyses in the cerebellum. RESULTS: We found that VH severity positively correlated with left lSTG-frontoparietal network FC, while it negatively correlated with FC between left lSTG and both cerebral and cerebellar representations of the default mode network. VH severity was not predicted by FC of left HG or right AC subregions. CONCLUSIONS: Our findings point to altered interactions between auditory perceptual processing and higher-level processes related to self-reference and executive functioning. This is the first study to show alterations in auditory cortical connectivity in trauma-related VH. While VH in trauma-D appears to be mediated by brain networks that are also implicated in schizophrenia VH, the results suggest a unique mechanism that could distinguish VH in trauma-D.

One-Pot Hydrothermal-Derived rGO/MXene/Sulfur Composite Aerogels as Free-Standing Cathodes in Lithium-Sulfur Batteries.

The confinement and high utilization of sulfur in the cathodes is critical for improved cycling performance of lithium-sulfur batteries. In this case one-pot hydrothermal strategy is developed to produce rGO/MXene/sulfur composite aerogels where sulfur is in situ trapped in the 3D rGO/MXene conductive skeleton. The optimized composite aerogels as free-standing cathodes delivery a specific capacity of 951 mAhg-1 after 100 cycles at 0.2 C with a low fading rate of 0.062 % per cycle. The excellent cycling performance is correlated with highly oxidized MXene and in situ formed sulfate/thiosulfate complex layer in the long-term cycles.

Verbal memory network mapping in individual patients predicts postoperative functional impairments.

Verbal memory decline is a significant concern following temporal lobe surgeries in patients with epilepsy, emphasizing the need for precision presurgical verbal memory mapping to optimize functional outcomes. However, the inter-individual variability in functional networks and brain function-structural dissociations pose challenges when relying solely on group-level atlases or anatomical landmarks for surgical guidance. Here, we aimed to develop and validate a personalized functional mapping technique for verbal memory using precision resting-state functional MRI (rs-fMRI) and neurosurgery. A total of 38 patients with refractory epilepsy scheduled for surgical interventions were enrolled and 28 patients were analyzed in the study. Baseline 30-min rs-fMRI scanning, verbal memory and language assessments were collected for each patient before surgery. Personalized verbal memory networks (PVMN) were delineated based on preoperative rs-fMRI data for each patient. The accuracy of PVMN was assessed by comparing post-operative functional impairments and the overlapping extent between PVMN and surgical lesions. A total of 14 out of 28 patients experienced clinically meaningful declines in verbal memory after surgery. The personalized network and the group-level atlas exhibited 100% and 75.0% accuracy in predicting postoperative verbal memory declines, respectively. Moreover, six patients with extra-temporal lesions that overlapped with PVMN showed selective impairments in verbal memory. Furthermore, the lesioned ratio of the personalized network rather than the group-level atlas was significantly correlated with postoperative declines in verbal memory (personalized networks: r = -0.39, p = .038; group-level atlas: r = -0.19, p = .332). In conclusion, our personalized functional mapping technique, using precision rs-fMRI, offers valuable insights into individual variability in the verbal memory network and holds promise in precision verbal memory network mapping in individuals.

Personalised functional imaging-guided multitarget continuous theta burst stimulation for post-stroke aphasia: study protocol for a randomised controlled trial.

INTRODUCTION: Continuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of post-stroke aphasia (PSA) patients shows promising results in clinical trials. However, existing PSA studies have focused on single-target rTMS, leaving unexplored the potential benefits of multitarget brain stimulation. Consequently, there is a need for a randomised clinical trial aimed to evaluate the efficacy and safety of cTBS targeting on multiple critical nodes in the language network for PSA. METHODS AND ANALYSIS: This is a prospective, multicentre, double-blind, two-arm parallel-group, sham-controlled randomised trial. The study will include a total of 60 participants who will be randomly assigned in a 1:1 ratio to either the active cTBS group or the sham cTBS group. Using precision resting-state functional MRI for each participant, we will map personalised language networks and design personalised targets in the inferior frontal gyrus, superior temporal gyrus and superior frontal gyrus. Participants will undergo a 3-week cTBS intervention targeting the three personalised targets, coupled with speech and language therapy. The primary outcome is the change in the Western Aphasia Battery-Revised aphasia quotient score among participants after a 3-week treatment. Secondary outcomes include Boston Diagnostic Aphasia Examination severity ratings, Token Test and the Chinese-version of the Stroke and Aphasia Quality of Life Scale 39-generic version. ETHICS AND DISSEMINATION: The study has been approved by the ethics committees of Affiliated Hospital of Hebei University, Hebei General Hospital and Affiliated Hospital of Chengde Medical University. The findings of this study will be reported in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: The study has been registered on ClinicalTrials.gov (NCT05957445).

Effects of polysaccharides on colonic targeting and colonic fermentation of ovalbumin-ferulic acid based emulsion.

Rutin is a polyphenol with beneficial pharmacological properties. However, its bioavailability is often compromised due to low solubility and poor stability. Encapsulation technologies, such as emulsion systems, have been proven to be promising delivery vehicles for enhancing the bioavailability of bioactive compounds. Thus, this study was proposed and designed to investigate the colonic targeting and colonic fermentation characteristics of rutin-loaded ovalbumin-ferulic acid-polysaccharide (OVA-FA-PS) complex emulsions. The results indicate that OVA-FA-PS emulsion effectively inhibits the degradation of rutin active substances and facilitates its transport of rutin to the colon. The analysis revealed that the OVA-FA-κ-carrageenan emulsion loaded with rutin exhibited superior elasticity and colon targeting properties compared to the OVA-FA-hyaluronic acid or OVA-FA-sodium alginate emulsions loaded with rutin in the composite emulsion. Additionally, it was observed that the rutin loaded within the OVA-FA-κ-carrageenan emulsion underwent degradation and was converted to 4-hydroxybenzoic acid during colonic fermentation.

SUGAR: Spherical ultrafast graph attention framework for cortical surface registration.

Cortical surface registration plays a crucial role in aligning cortical functional and anatomical features across individuals. However, conventional registration algorithms are computationally inefficient. Recently, learning-based registration algorithms have emerged as a promising solution, significantly improving processing efficiency. Nonetheless, there remains a gap in the development of a learning-based method that exceeds the state-of-the-art conventional methods simultaneously in computational efficiency, registration accuracy, and distortion control, despite the theoretically greater representational capabilities of deep learning approaches. To address the challenge, we present SUGAR, a unified unsupervised deep-learning framework for both rigid and non-rigid registration. SUGAR incorporates a U-Net-based spherical graph attention network and leverages the Euler angle representation for deformation. In addition to the similarity loss, we introduce fold and multiple distortion losses to preserve topology and minimize various types of distortions. Furthermore, we propose a data augmentation strategy specifically tailored for spherical surface registration to enhance the registration performance. Through extensive evaluation involving over 10,000 scans from 7 diverse datasets, we showed that our framework exhibits comparable or superior registration performance in accuracy, distortion, and test-retest reliability compared to conventional and learning-based methods. Additionally, SUGAR achieves remarkable sub-second processing times, offering a notable speed-up of approximately 12,000 times in registering 9,000 subjects from the UK Biobank dataset in just 32 min. This combination of high registration performance and accelerated processing time may greatly benefit large-scale neuroimaging studies.

Individualized Functional Brain System Topologies and Major Depression: Relationships Among Patch Sizes and Clinical Profiles and Behavior.

BACKGROUND: Neuroimaging studies of major depression have typically been conducted using group-level approaches. However, given interindividual differences in brain systems, there is a need for individualized approaches to brain systems mapping and putative links toward diagnosis, symptoms, and behavior. METHODS: We used an iterative parcellation approach to map individualized brain systems in 328 participants from a multisite, placebo-controlled clinical trial. We hypothesized that participants with depression would show abnormalities in salience, control, default, and affective systems, which would be associated with higher levels of self-reported anhedonia, anxious arousal, and worse cognitive performance. Within hypothesized brain systems, we compared patch sizes (number of vertices) between depressed and healthy control groups. Within depressed groups, abnormal patches were correlated with hypothesized clinical and behavioral measures. RESULTS: Significant group differences emerged in hypothesized patches of 1) the lateral salience system (parietal operculum; t326 = -3.11, p = .002) and 2) the control system (left medial posterior prefrontal cortex region; z = -3.63, p < .001), with significantly smaller patches in these regions in participants with depression than in healthy control participants. Results suggest that participants with depression with significantly smaller patch sizes in the lateral salience system and control system regions experience greater anxious arousal and cognitive deficits. CONCLUSIONS: The findings imply that neural features mapped at the individual level may relate meaningfully to diagnosis, symptoms, and behavior. There is strong clinical relevance in taking an individualized brain systems approach to mapping neural functional connectivity because these associated region patch sizes may help advance our understanding of neural features linked to psychopathology and foster future patient-specific clinical decision making.

Individualized functional connectivity markers associated with motor and mood symptoms of Parkinson's disease.

Parkinson's disease (PD) is a complex neurological disorder characterized by many motor and non-motor symptoms. While most studies focus on the motor symptoms of the disease, it is important to identify markers that underlie different facets of the disease. In this case-control study, we sought to discover reliable, individualized functional connectivity markers associated with both motor and mood symptoms of PD. Using functional MRI, we extensively sampled 166 patients with PD (64 women, 102 men; mean age=61.8 years, SD=7.81) and 51 healthy control participants (32 women, 19 men; mean age=55.68 years, SD=7.62). We found that a model consisting of 44 functional connections predicted both motor (UPDRS-III: Pearson r=0.21, FDR-adjusted p=0.006) and mood symptoms (HAMD: Pearson r=0.23, FDR-adjusted p=0.006; HAMA: Pearson r=0.21, FDR-adjusted p=0.006). Two sets of connections contributed differentially to these predictions. Between-network connections, mainly connecting the sensorimotor and visual large-scale functional networks, substantially contributed to the prediction of motor measures, while within-network connections in the insula and sensorimotor network contributed more so to mood prediction. The middle to posterior insula region played a particularly important role in predicting depression and anxiety scores. We successfully replicated and generalized our findings in two independent PD datasets. Taken together, our findings indicate that sensorimotor and visual network markers are indicative of PD brain pathology, and that distinct subsets of markers are associated with motor and mood symptoms of PD.

Effects of a periodic intermittent theta burst stimulation in Alzheimer's disease.

Background: Previous studies have demonstrated that excitatory repetitive transcranial magnetic stimulation (rTMS) can improve the cognitive function of patients with Alzheimer's disease (AD). Intermittent theta burst stimulation (iTBS) is a novel excitatory rTMS protocol for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for AD. However, the long-term effects of iTBS on cognitive decline and brain structure in patients with AD are unknown. Aims: We aimed to explore whether repeating accelerated iTBS every three months could slow down the cognitive decline in patients with AD. Methods: In this randomised, assessor-blinded, controlled trial, iTBS was administered to the left dorsolateral prefrontal cortex (DLPFC) of 42 patients with AD for 14 days every 13 weeks. Measurements included the Montreal Cognitive Assessment (MoCA), a comprehensive neuropsychological battery, and the grey matter volume (GMV) of the hippocampus. Patients were evaluated at baseline and after follow-up. The longitudinal pipeline of the Computational Anatomy Toolbox for SPM was used to detect significant treatment-related changes over time. Results: The iTBS group maintained MoCA scores relative to the control group (t=3.26, p=0.013) and reduced hippocampal atrophy, which was significantly correlated with global degeneration scale changes. The baseline Mini-Mental State Examination (MMSE) score, apolipoprotein E genotype and Clinical Dementia Rating were indicative of MoCA scores at follow-up. Moreover, the GMV of the left (t=0.08, p=0.996) and right (t=0.19, p=0.977) hippocampus were maintained in the active group but significantly declined in the control group (left: t=4.13, p<0.001; right: t=5.31, p<0.001). GMV change in the left (r=0.35, p=0.023) and right (r=0.36, p=0.021) hippocampus across the intervention positively correlated with MoCA changes; left hippocampal GMV change was negatively correlated with global degeneration scale (r=-0.32, p=0.041) changes. Conclusions: DLPFC-iTBS may be a feasible and easy-to-implement non-pharmacological intervention to slow down the progressive decline of overall cognition and quality of life in patients with AD, providing a new AD treatment option. Trial registration number: NCT04754152.

Finite Element Analysis of the Effect for Different Thicknesses and Stitching Densities under the Low-Velocity Impact of Stitched Composite Laminates.

In this study, a progressive damage model was developed for the mechanical response and damage evolution of carbon fiber stitched composite laminates under low-velocity impact (LVI). The three-dimensional Hashin and Hou failure criteria were used to identify fiber and matrix damage. The cohesive zone model was adopted to simulate the delamination damage, combined with the linear degradation discounting of the equivalent displacement method to characterize the stiffness degradation of the material, and the corresponding user material subroutine VUMAT was coded. The finite element analysis of the LVI of stitched composite laminates under different energies was finished in Abaqus/Explicit. Furthermore, the simulation predictions matched well with the results of the experimental tests. Based on this, composite laminates' mechanical response and damage forms with different thicknesses and stitch densities were analyzed. The findings show that the main damages of composite laminates were matrix tensile damage and delamination. The stitching process could improve the impact tolerance of composite laminates, inhibiting delamination and reducing the area of the delamination damage. The higher the density of the stitching, the more noticeable its inhibition would be. The thickness of the laminate also had a more significant effect on the damage to the laminate. Thin plates were more prone to matrix tensile damage due to their lower flexural rigidity, whereas thick plates were more susceptible to delamination because of their higher flexural rigidity.