Hippocampal connectivity patterns echo macroscale cortical evolution in the primate brain.

While the hippocampus is key for human cognitive abilities, it is also a phylogenetically old cortex and paradoxically considered evolutionarily preserved. Here, we introduce a comparative framework to quantify preservation and reconfiguration of hippocampal organisation in primate evolution, by analysing the hippocampus as an unfolded cortical surface that is geometrically matched across species. Our findings revealed an overall conservation of hippocampal macro- and micro-structure, which shows anterior-posterior and, perpendicularly, subfield-related organisational axes in both humans and macaques. However, while functional organisation in both species followed an anterior-posterior axis, we observed a marked reconfiguration in the latter across species, which mirrors a rudimentary integration of the default-mode-network in non-human primates. Here we show that microstructurally preserved regions like the hippocampus may still undergo functional reconfiguration in primate evolution, due to their embedding within heteromodal association networks.

National rollout of a medication safety dashboard to improve testing for latent infections among biologic and targeted synthetic disease-modifying agent users within the Veterans Health Administration.

OBJECTIVE: To develop, deploy, and evaluate a national, electronic health record (EHR)-based dashboard to support safe prescribing of biologic and targeted synthetic disease-modifying agents (b/tsDMARDs) in the United States Veterans Affairs Healthcare System (VA). DATA SOURCES AND STUDY SETTING: We extracted and displayed hepatitis B (HBV), hepatitis C (HCV), and tuberculosis (TB) screening data from the EHR for users of b/tsDMARDs using PowerBI (Microsoft) and deployed the dashboard to VA facilities across the United States in 2022; we observed facilities for 44 weeks post-deployment. STUDY DESIGN: We examined the association between dashboard engagement by healthcare personnel and the percentage of patients with all screenings complete (HBV, HCV, and TB) at the facility level using an interrupted time series. Based on frequency of sessions, facilities were grouped into high- and low/none-engagement categories. We modeled changes in complete screening pre- and post-deployment of the dashboard. DATA COLLECTION METHODS: All VA facilities were eligible for inclusion; excluded facilities participated in design of the dashboard or had <20 patients receiving b/tsDMARDs. Session counts from facility personnel were captured using PowerBI audit log data. Outcomes were assessed weekly based on EHR data extracted via the dashboard itself. PRINCIPAL FINDINGS: Totally 117 facilities (serving a total of 41,224 Veterans prescribed b/tsDMARDs) were included. Before dashboard deployment, across all facilities, 61.5% of patients had all screenings complete, which improved to 66.3% over the course of the study period. The largest improvement (15 percentage points, 60.3%-75.3%) occurred among facilities with high engagement (post-intervention difference in outcome between high and low/none-engagement groups was 0.17 percentage points (pp) per week, 95% confidence interval (0.04 pp, 0.30 pp); p = 0.01). CONCLUSIONS: We observed significant improvements in screening for latent infections among facilities with high engagement with the dashboard, compared with those with fewer sessions.

TDP-43-M323K causes abnormal brain development and progressive cognitive and motor deficits associated with mislocalised and increased levels of TDP-43.

TDP-43 pathology is found in several neurodegenerative disorders, collectively referred to as "TDP-43 proteinopathies". Aggregates of TDP-43 are present in the brains and spinal cords of >97% of amyotrophic lateral sclerosis (ALS), and in brains of ∼50% of frontotemporal dementia (FTD) patients. While mutations in the TDP-43 gene (TARDBP) are usually associated with ALS, many clinical reports have linked these mutations to cognitive impairments and/or FTD, but also to other neurodegenerative disorders including Parkinsonism (PD) or progressive supranuclear palsy (PSP). TDP-43 is a ubiquitously expressed, highly conserved RNA-binding protein that is involved in many cellular processes, mainly RNA metabolism. To investigate systemic pathological mechanisms in TDP-43 proteinopathies, aiming to capture the pleiotropic effects of TDP-43 mutations, we have further characterised a mouse model carrying a point mutation (M323K) within the endogenous Tardbp gene. Homozygous mutant mice developed cognitive and behavioural deficits as early as 3 months of age. This was coupled with significant brain structural abnormalities, mainly in the cortex, hippocampus, and white matter fibres, together with progressive cortical interneuron degeneration and neuroinflammation. At the motor level, progressive phenotypes appeared around 6 months of age. Thus, cognitive phenotypes appeared to be of a developmental origin with a mild associated progressive neurodegeneration, while the motor and neuromuscular phenotypes seemed neurodegenerative, underlined by a progressive loss of upper and lower motor neurons as well as distal denervation. This is accompanied by progressive elevated TDP-43 protein and mRNA levels in cortex and spinal cord of homozygous mutant mice from 3 months of age, together with increased cytoplasmic TDP-43 mislocalisation in cortex, hippocampus, hypothalamus, and spinal cord at 12 months of age. In conclusion, we find that Tardbp M323K homozygous mutant mice model many aspects of human TDP-43 proteinopathies, evidencing a dual role for TDP-43 in brain morphogenesis as well as in the maintenance of the motor system, making them an ideal in vivo model system to study the complex biology of TDP-43.

Thermal stimulus task fMRI in the cervical spinal cord at 7 Tesla.

Although functional magnetic resonance imaging (fMRI) is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0 . Increasing field strength enables higher spatial resolution and improved sensitivity to blood oxygenation level-dependent (BOLD) signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D echo-planar imaging (EPI) protocols, which differ in sensitivity to spatial and temporal B0 inhomogeneity. The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. All protocols used 3 mm slice thickness. For each protocol, the BOLD response to 13 10-s noxious thermal stimuli applied to the right thumb was acquired in a 10-min fMRI run. Image quality, temporal signal to noise ratio (SNR), and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment. PRACTITIONER POINTS: First stimulus task fMRI results in the spinal cord at 7 T. Single-shot 0.75 mm 2D EPI produced the highest mean z-statistic. Multi-shot 0.60 mm 2D EPI provided the best-localized activation and least distortion.

National Survey of the Bone Densitometry Evaluation Process Within an Integrated Healthcare System.

BACKGROUND: To assess the current state of bone mineral density evaluation services via dual energy x-ray absorptiometry (DXA) provided to Veterans with fracture risk through the development and administration of a nationwide survey of facilities in the Veterans Health Administration. METHODOLOGY: The Bone Densitometry Survey was developed by convening a Work Group of individuals with expertise in bone densitometry and engaging the Work Group in an iterative drafting and revision process. Once completed, the survey was beta tested, administered through REDCap, and sent via e-mail to points of contact at 178 VHA facilities. RESULTS: Facility response rate was 31 % (56/178). Most DXA centers reported positively to markers of readiness for their bone densitometers: less than 10 years old (n=35; 63 %); in "excellent" or "good" condition (n=44; 78 %, 32 % and 46 %, respectively); and perform phantom calibration (n=43; 77 %). Forty-one DXA centers (73 %) use intake processes that have been shown to reduce errors. Thirty-seven DXA centers (66 %) reported their technologists receive specialized training in DXA, while 14 (25 %) indicated they receive accredited training. Seventeen DXA centers (30 %) reported performing routine precision assessment. CONCLUSIONS: Many DXA centers reported using practices that meet minimal standards for DXA reporting and preparation; however, the lack of standardization, even within an integrated healthcare system, indicates an opportunity for quality improvement to ensure consistent high quality bone mineral density evaluation of Veterans.