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Bollinger, L.

Publications and source records attributed to Bollinger, L..

2 recordsLinked to original sources

Frontoparietal effective connectivity supports working memory in early childhood

Working memory (WM), a core executive function that supports learning and reasoning, undergoes rapid development during early childhood years. Neural activation patterns underlying WM have been extensively studied in both adults and children, revealing increasing involvement of the frontoparietal network (FPN) with age and coordinated interactions with the default mode network (DMN). However, relatively little is known about how these network interactions develop in children, particularly within the visuospatial domain. The present study investigated the influence of age and task performance on effective connectivity within the FPN and its interactions with DMN hubs during a visuospatial WM task in early childhood. Functional MRI data were collected during a visual n-back task with two WM load levels (0-back and 2-back) in 120 typically developing children aged 5-8 years. Dynamic Causal Modeling (DCM) with parametric empirical Bayes was used to estimate effective connectivity among eight regions of interest spanning the FPN and DMN. Behaviorally, age-related gains were steepest under high-load for accuracy, and under low-load for reaction time, suggesting WM capacity is a demand-sensitive marker of development at this age. At the network level, high-load robustly engaged the FPN, whereas low-load was associated with relatively greater engagement of DMN and episodic memory-related regions. Baseline effective connectivity was dominated by parietal-to-frontal drive and strong self-inhibition in the anterior cingulate cortex. Age-related effects on this architecture were sparse, involving asymmetric interhemispheric frontal coupling and reduced parieto-cingulate coupling, whereas accuracy-related effects were larger in magnitude, particularly at self-connections. More accurate children showed greater excitability in frontal and parietal FPN nodes alongside increased self-inhibition in the precuneus, a DMN hub, consistent with a neural efficiency account in which better performance reflects more selective, rather than more global, network engagement. Task load further shaped connectivity in distinct ways: low-load elicited widespread inter-regional modulation, whereas high-load predominantly modulated self-connections, with age and accuracy effects on this modulation dissociating by load. These findings suggest that, in primary school children, current task performance was associated with more pronounced differences in frontoparietal effective connectivity than was age, and that WM-related network engagement becomes increasingly selective and load-dependent across this developmental window.

neuroscience↗

An emergent Ebola virus nucleoprotein variant influences virion budding, oligomerization, transcription and replication

For highly pathogenic viruses, reporter assays that can be rapidly performed are critically needed to identify potentially functional mutations for further study under maximal containment (e.g., biosafety level 4 [BSL-4]). The Ebola virus nucleoprotein (NP) plays multiple essential roles during the viral life cycle, yet few tools exist to study the protein under BSL-2 or equivalent containment. Therefore, we adapted reporter assays to measure NP oligomerization and virion-like particle (VLP) production in live cells and further measure transcription and replication using established minigenome assays. As a proof-of-concept, we examined the NP-R111C substitution, which emerged during the 2013-2016 Western African Ebola virus disease epidemic and rose to high frequency. NP-R111C slightly increased NP oligomerization and VLP budding but slightly decreased transcription and replication. By contrast, a synthetic charge-reversal mutant, NP-R111E, greatly increased oligomerization but abrogated transcription and replication. These results are intriguing in light of recent structures of NP oligomers, which reveal that the neighboring residue, K110, forms a salt bridge with E349 on adjacent NP molecules. By developing and utilizing multiple reporter assays, we find that the NP-111 position mediates a complex interplay between NPs roles in protein structure, virion budding, and transcription and replication.

microbiology↗