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Strahnen, D.

Publications and source records attributed to Strahnen, D..

3 recordsLinked to original sources

Riboflavin-sensitized UVA collagen crosslinking produced a controllable, dose-dependent increase in the nanomechanical strength of ex vivo bovine dura mater

BackgroundDural defects, either from trauma, tumor resection, surgical approaches, genetics, or spontaneously represent a significant clinical challenge in neurosurgery. Given the established efficacy of riboflavin-sensitized ultraviolet-A (UVA) photo-crosslinking in ophthalmology, this study investigated its feasibility and dose-response characteristics as a novel strategy to biochemically augment the mechanical integrity and strength of ex-vivo bovine dura mater. MethodsForty bovine dura mater specimens were treated ex vivo using riboflavin concentrations of 2, 4, or 8 mM combined with UVA irradiation at 0.3 or 3 mW/cm{superscript 2}. PBS-treated specimens exposed to UVA served as controls. Atomic force microscopy nanoindentation was used to measure the local elastic modulus in matched regions before and after treatment, enabling paired assessment of treatment-induced mechanical changes while minimizing inter-sample variability. Post-treatment stiffness, fold-change from baseline, and riboflavin dose-response relationships were analyzed statistically. ResultsBaseline elastic moduli were equivalent across all groups (mean approximately 52 kPa, p=0.92). While UVA alone caused a modest approximately 2- to 3-fold stiffness increase, riboflavin-UVA treatment produced a dramatic, concentration-dependent effect. The highest treatment (8 mM RF, 3 mW/cm{superscript 2} UVA) increased the elastic modulus 150-fold, from approximately 53 kPa to approximately 8,000 kPa. Post-UV stiffness exhibited a strong linear relationship with riboflavin concentration (R{superscript 2} = 0.994), indicating a precisely titratable crosslinking effect. All treatment conditions were statistically distinguishable (p < 0.001). ConclusionRiboflavin-sensitized UVA crosslinking substantially increases the nanomechanical strength of ex vivo bovine dura mater in a controllable, dose-dependent manner. These findings establish a proof of concept for biochemical reinforcement of dural tissue that might be used clinically. As a next step evaluation using human dura, macroscopic biomechanical testing, penetration-depth analysis, and safety assessment is warranted.

bioengineering↗

Highly task-specific and distributed neural connectivity in working memory revealed by single-trial decoding in mice and humans

Working memory (WM), the capacity to briefly and intentionally maintain mental items, is key to successful goal-directed behaviour and impaired in a range of psychiatric disorders. To date, several brain regions, connections, and types of neural activity have been correlatively associated with WM performance. However, no unifying framework to integrate these findings exits, as the degree of their species- and task-specificity remains unclear. Here, we investigate WM correlates in three task paradigms each in mice and humans, with simultaneous multi-site electrophysiological recordings. We developed a machine learning-based approach to decode WM-mediated choices in individual trials across subjects from hundreds of electrophysiological measures of neural connectivity with up to 90% prediction accuracy. Relying on predictive power as indicator of correlates of psychological functions, we unveiled a large number of task phase-specific WM-related connectivity from analysis of predictor weights in an unbiased manner. Only a few common connectivity patterns emerged across tasks. In rodents, these were thalamus-prefrontal cortex delta- and beta-frequency connectivity during memory encoding and maintenance, respectively, and hippocampal-prefrontal delta- and theta-range coupling during retrieval, in rodents. In humans, task-independent WM correlates were exclusively in the gamma-band. Mostly, however, the predictive activity patterns were unexpectedly specific to each task and always widely distributed across brain regions. Our results suggest that individual tasks cannot be used to uncover generic physiological correlates of the psychological construct termed WM and call for a new conceptualization of this cognitive domain in translational psychiatry.

neuroscience↗

Lack of redundancy between electrophysiological measures of long-range neuronal communication

Communication between brain areas has been implicated in a wide range of cognitive and emotive functions and is impaired in numerous mental disorders. In rodent models, various functional connectivity metrics have been used to quantify inter-regional neuronal communication. However, in individual studies, typically only very few measures of coupling are reported and, hence, redundancy across such indicators is implicitly assumed. In order to test this assumption, we here comparatively assessed a broad range of directional and non-directional metrics like coherence, weighted Phase-Lag-Index (wPLI), Granger causality (GC), spike-phase coupling (SPC), cross-regional phase-amplitude coupling, amplitude cross-correlations, and others. We applied these analyses to simultaneous field recordings from the prefrontal cortex and the ventral and dorsal hippocampus in the schizophrenia-related Gria1-knockout mouse model which displays a robust novelty-induced hyperconnectivity phenotype. We find that across such measures there is a considerable lack of functional redundancy. While coherence and GC yielded similar results, other measures, especially wPLI and SPC, often produced deviating conclusions. Bivariate correlations within animals revealed that virtually none of the metrics consistently co-varied with any of the other measures across the three connections and two genotypes analysed. Parametric GC showed the qualitatively highest degree of redundancy with other metrics and would be most suitable for connectivity analysis. We conclude that analysis of multiple metrics is necessary to characterise functional connectivity.

neuroscience↗