Explore the vast range of titles available.

Language abilities are known to deteriorate in aging, possibly related to decreased functional and structural connectivity within specialized brain networks. Here, we investigated syntactic ability in healthy young and older adults using a comprehensive assessment of behavioral performance, task-independent functional (FC) and structural brain connectivity (SC). Seed-based FC originating from left pars opercularis (part of Broca's area) known to support syntactic processes was assessed using resting-state functional magnetic resonance imaging, and SC using fractional anisotropy from diffusion weighted imaging, in the dorsally located superior longitudinal and the ventrally located uncinate fasciculi (SLF, UF) and forceps minor. Young compared to older adults exhibited superior syntactic performance and stronger FC within the mainly left-lateralized syntax network, which was beneficial for performance. In contrast, in older adults, FC within the mainly left-lateralized syntax network was reduced and did not correlate with performance; inter-hemispheric FC to right inferior frontal and angular gyri was detrimental for performance. In both groups, performance was positively correlated with inter-hemispheric SC. For intra-hemispheric SC, performance correlated with structural integrity of SLF in young adults and with integrity of UF in older adults. Our data show that reduced syntactic ability in older adults is associated with decreased FC within dedicated syntax networks. Moreover, young adults showed an association of syntactic ability with structural integrity of the dorsal tract, while older adults rely more on ventral fibers. In sum, our study provided novel insight into the relationship between connectivity and syntactic performance in young and older adults. In addition to elucidating age-related changes in syntax networks and their behavioral relevance, our results contribute to a better understanding of age-related changes in functional and structural brain organization in general, an important prerequisite for developing novel strategies to counteract age-related cognitive decline. •Syntax networks differ between older and young adults.•Functional connectivity within syntax networks correlates with performance.•Inter- and intra-hemispheric structural connectivity is associated with performance.•Young adults rely on dorsal, older adults on ventral language pathways.

The relationship between brain structure, cortical physiology, and learning ability in older adults is of particular interest in understanding mechanisms of age-related cognitive decline. Only a few studies addressed this issue so far, yielding mixed results. Here, we used comprehensive multiple regression analyses to investigate associations between brain structure on the one hand, i.e., cortical thickness (CT), fractional anisotropy (FA) of the pyramidal tract and individual coil-to-cortex distance, and cortical physiology on the other hand, i.e. motor cortex excitability and long-term potentiation (LTP)-like cortical plasticity, in healthy older adults (mean age 64years, 14 women). Additional exploratory analyses assessed correlations between cortical physiology and learning ability in the verbal domain. In the regression models, we found that cortical excitability could be best predicted by CT of the hand knob of the primary motor cortex (CT-M1HAND) and individual coil-to-cortex distance, while LTP-like cortical plasticity was predicted by CT-M1HAND and FA of the pyramidal tract. Exploratory analyses revealed a significant inverse correlation between cortical excitability and learning ability. In conclusion, higher cortical excitability was associated with lower CT and lower learning ability in a cohort of healthy older adults, in line with previous reports of increased cortical excitability in patients with cortical atrophy and cognitive deficits due to Alzheimer's Disease. Cortical excitability may thus be a parameter to identify individuals at risk for cognitive decline and gray matter atrophy, a hypothesis to be explored in future longitudinal studies. •Associations between brain structure (MRI) and cortical physiology (TMS).•Higher cortical excitability was associated with lower CT in healthy older adults.•Cortical LTP-like plasticity was dependent on structural integrity of the pyramidal tract.•Subjects with higher cortical excitability revealed lower learning ability.•TMS may help to identify patients at risk for developing dementia.

The single nucleotide polymorphism rs17070145 within the KIBRA gene (kidney and brain expressed protein) has been associated with variations in memory functions and related brain areas. However, previous studies yielded conflicting results, which might be due to divergent sample characteristics or task-specific effects. Therefore, we aimed to determine the impact of KIBRA genotype on learning and memory formation, and volume, microstructural integrity and functional connectivity (FC) of the hippocampus and its subfields in a well-characterized cohort of healthy older adults. One-hundred and forty subjects (72 women, age 50-80) were KIBRA genotyped and memory was tested using the Auditory Verbal Learning Task. Also, subjects underwent structural and resting-state functional magnetic resonance imaging at 3T. Subfields were delineated using automated segmentation (FreeSurfer software). Microstructural integrity was measured using mean diffusivity (MD) derived from diffusion tensor images. Seed-based analyses were used to assess FC patterns of the hippocampus. KIBRA T-allele carriers showed a trend for better memory performance, and in the hippocampus significantly higher volumes and partly lower MD, indicative for better microstructure, compared with non-T-allele carriers in the cornu ammonis (CA)2/3 and CA4/dentate gyrus subfields (all P⩽0.008, Bonferroni corrected). Also, T-allele carriers exhibited lower FC of the left hippocampus with areas outside the synchronized HC network. In sum, we could show for the first time that older T-allele carriers exhibited larger volumes and better microstructure within those hippocampus subfields that are implicated in long-term potentiation and neurogenesis, key features of memory processes. Moreover, T-allele carriers showed a more selective FC network of the hippocampus.

INTRODUCTION While incident ischemic lesions (IILs) are not unusual on follow‐up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown. METHODS In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months. RESULTS At 6 months, 78 patients (15.5%) had IILs, mostly diffusion‐weighted imaging‐positive (72%) and clinically covert (91%). Older age and small vessel disease (SVD) lesions were baseline risk factors for IILs. IILs were associated with worse cognitive (beta for global cognition: −0.31, 95% confidence interval [CI]: −0.48 to −0.14) and functional outcomes (beta for modified Rankin scale [mRS]: 0.36, 95% CI: 0.14 to 0.58), and higher recurrent stroke risk (hazard ratio: 3.81, 95% CI: 1.35 to 10.69). IILs partially explained the relationship between SVD and poor cognition. DISCUSSION IILs are common and are associated with worse cognitive and functional outcomes and stroke recurrence risk. Assessing IILs following stroke might aid prognostication. Highlights Incident ischemic lesions (IILs) were assessed with registered baseline and 6‐month magnetic resonance imaging (MRI) scans in a stroke cohort. IILs 6 months after stroke are present in one‐sixth of patients and are mostly clinically silent. Small vessel disease burden is the main baseline risk factor for IILs. IILs are associated with cognitive and functional impairment and stroke recurrence. Assessing IILs by follow‐up MRI aids long‐term prognostication for stroke patients.

The viral genome of the SARS-CoV-2 coronavirus, the aetiologic agent of COVID-19, encodes structural, non-structural, and accessory proteins. Most of these components undergo rapid genetic variations, though to a lesser extent the essential viral proteases. Consequently, the protease and/or deubiquitinase activities of the cysteine proteases M and PL became attractive targets for the design of antiviral agents. Here, we develop and evaluate new bis(benzylidene)cyclohexanones (BBC) and identify potential antiviral compounds. Three compounds were found to be effective in reducing the SARS-CoV-2 load, with EC values in the low micromolar concentration range. However, these compounds also exhibited inhibitory activity IC against PL at approximately 10-fold higher micromolar concentrations. Although originally developed as PL inhibitors, the comparison between IC and EC of BBC indicates that the mechanism of their antiviral activity is probably not directly related to inhibition of viral cysteine proteases. In conclusion, our study has identified new potential noncytotoxic antiviral compounds suitable for testing and further improvement.